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Li D, Xie Z, Shaikh SB, Rahman I. Altered expression profile of plasma exosomal microRNAs in exclusive electronic cigarette adult users. Sci Rep 2025; 15:2714. [PMID: 39837838 PMCID: PMC11751386 DOI: 10.1038/s41598-025-85373-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Accepted: 01/02/2025] [Indexed: 01/23/2025] Open
Abstract
Little is known about how exclusive e-cigarette use affects exosomal microRNA (miRNA) expression, which is crucial in inflammation and disease processes like cancer. We compared exosomal miRNA profiles between exclusive e-cigarette users and non-users. We used plasma samples from 15 exclusive e-cigarette users and 15 non-users from the Population Assessment of Tobacco and Health (PATH) Wave 1 study (2013-2014) and sequenced miRNAs with Illumina NextSeq 500/550. We performed differential analyses using DESeq2 in R/Bioconductor, adjusting for race, and conducted gene enrichment analyses on target genes regulated by significant miRNAs. Further, molecular-based techniques using the miRNA mimics and inhibitors were applied for the validation of the expressions of the miRNAs in vitro. We identified four miRNAs that were upregulated in exclusive e-cigarette users compared to non-users: hsa-miR-100-5p, hsa-miR-125a-5p, hsa-miR-125b-5p, and hsa-miR-99a-5p, after adjusting for the confounding effects of race. However, none of the miRNAs remained statistically significant after controlling for the false discovery rate (FDR) at 5%. Subgroup analysis of White participants only identified four miRNAs (hsa-miR-100-5p, hsa-miR-125b-5p, hsa-miR-200b-3p, and hsa-miR-99a-5p) that were also upregulated in e-cigarette users with one miRNA hsa-miR-200b-3p remaining statistical significance after controlling for the FDR at 5%. GO enrichment analysis showed that these miRNAs are involved in processes like transcription regulation and cellular protein modification. KEGG pathway analysis indicated their involvement in cancer pathways, including small cell lung cancer, renal cell carcinoma, and signaling pathways (neurotrophin, ErbB, PI3K-Akt, FoxO, Hippo, MAPK, TGF-beta). Overexpression of hsa-miR-125b-5p promoted DNA damage in bronchial epithelial cells. These findings suggest an elevation of carcinogenic cellular signaling pathways in exclusive e-cigarette users.
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Affiliation(s)
- Dongmei Li
- Department of Clinical and Translational Research, University of Rochester Medical Center, Rochester, NY, US.
| | - Zidian Xie
- Department of Clinical and Translational Research, University of Rochester Medical Center, Rochester, NY, US
| | - Sadiya Bi Shaikh
- Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY, US
| | - Irfan Rahman
- Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY, US
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Li D, Xie Z, Shaikh SB, Rahman I. Abnormal expression profile of plasma exosomal microRNAs in exclusive electronic cigarette adult users. RESEARCH SQUARE 2024:rs.3.rs-3877316. [PMID: 38343804 PMCID: PMC10854321 DOI: 10.21203/rs.3.rs-3877316/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/18/2024]
Abstract
Background Exposure to electronic cigarette (e-cigarette) aerosol has been linked to several health concerns, including DNA damage, elevated oxidative stress, the release of inflammatory cytokine, and dysfunctions in epithelial barriers. However, little is known about the effect of exclusive e-cigarette use on expression profiles of exosomal miRNAs, which play critical regulatory roles in many inflammatory responses and disease processes including cancer. We aim to compare the exosomal microRNA expression profile between exclusive e-cigarette users and normal controls without any tobacco product use (non-users). Methods Using plasma samples from 15 exclusive e-cigarette users and 15 non-users in the Population Assessment of Tobacco and Health (PATH) Wave 1 study (2013-2014), we examined exosomal microRNAs expression levels through Illumina NextSeq 500/550 sequencing. The differential analyses between exclusive e-cigarette users and non-users were examined using the generalized linear model approach in the DESeq2 package in R/Bioconductor after adjusting the significant confounding effect from race. Gene enrichment analyses were conducted on target genes regulated by significant microRNAs in the differential analyses. Further, molecular-based techniques using the micro RNA mimics and inhibitors were applied for the validation of the expressions of the micro RNAs in vitro. Results We identified four microRNAs that have significantly higher expression levels in exclusive e-cigarette users than non-users including hsa-miR-100-5p, hsa-miR-125a-5p, hsa-miR-125b-5p, and hsa-miR-99a-5p. GO enrichment analysis on the target genes regulated by the four microRNAs showed that dysregulation of the four microRNAs in exclusive e-cigarette users involved in multiple cell processes such as protein kinase binding and miRNA metabolic process. KEGG pathway enrichment analysis found the four upregulated miRNAs in exclusive e-cigarette users involved in many cancer pathways such as the non-small cell lung cancer, small cell lung cancer, pancreatic cancer, p53 signaling pathway, Hippo signaling pathway, HIF-1 signaling pathway, and MAPK signaling pathway. Overexpression of miRNA hsa-miR-125b-5p was shown to promote DNA damage in bronchial epithelia cells. Conclusions Four plasma exosomal microRNAs involved in cancer development had higher expression levels in exclusive e-cigarette users than non-users, which might indicate a potentially elevated risk of cancer among exclusive e-cigarette users.
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Jiao Y, Mi S, Li X, Liu Y, Han N, Xu J, Liu Y, Li S, Guo L. MicroRNA-155 targets SOCS1 to inhibit osteoclast differentiation during orthodontic tooth movement. BMC Oral Health 2023; 23:955. [PMID: 38041017 PMCID: PMC10693016 DOI: 10.1186/s12903-023-03443-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Accepted: 09/21/2023] [Indexed: 12/03/2023] Open
Abstract
BACKGROUND MicroRNA-155 (miR-155) is a multifunctional miRNA whose expression is known to be involved in a range of physiological and pathological processes. Its association with several oral diseases has been established. However, the specific role of miR-155 in orthodontic tooth movement remains unclear. In this study, we investigated the impact of miR-155 on osteoclast differentiation and orthodontic tooth movement models, aiming to explore the underlying mechanisms. METHODS In this experiment, we utilized various agents including miR-155 mimic, miR-155 inhibitor, as well as non-specific sequences (NC mimic & NC inhibitor) to treat murine BMMNCs. Subsequently, osteoclast induction (OC) was carried out to examine the changes in the differentiation ability of monocytes under different conditions. To assess these changes, we employed RT-PCR, Western blotting, and TRAP staining techniques. For the orthodontic tooth movement model in mice, the subjects were divided into two groups: the NaCl group (injected with saline solution) and the miR-155 inhibitor group (injected with AntagomiR-155). We observed the impact of orthodontic tooth movement using stereoscopic microscopy, micro-CT, and HE staining. Furthermore, we performed RT-PCR and Western blotting analyses on the tissues surrounding the moving teeth. Additionally, we employed TargetScan to predict potential target genes of miR-155. RESULTS During osteoclast induction of BMMNCs, the expression of miR-155 exhibited an inverse correlation with osteoclast-related markers. Overexpression of miR-155 led to a decrease in osteoclast-related indexes, whereas underexpression of miR-155 increased those indexes. In the mouse orthodontic tooth movement model, the rate of tooth movement was enhanced following injection of the miR-155 inhibitor, leading to heightened osteoclast activity. TargetScan analysis identified SOCS1 as a target gene of miR-155. CONCLUSIONS Our results suggest that miR-155 functions as an inhibitor of osteoclast differentiation, and it appears to regulate osteoclasts during orthodontic tooth movement. The regulatory mechanism of miR-155 in this process involves the targeting of SOCS1.
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Affiliation(s)
- Yao Jiao
- Department of Periodontics, School of Stomatology, Capital Medical University, Tian Tan Xi Li No.4, Beijing, 100050, P. R. China
| | - Sicong Mi
- Department of Stomatology, Air Force Medical Center, PLA, The Fourth Military Medical University, Beijing, 100142, P. R. China
| | - Xiaoyan Li
- Department of Periodontics, School of Stomatology, Capital Medical University, Tian Tan Xi Li No.4, Beijing, 100050, P. R. China
- Laboratory of Tissue Regeneration and Immunology, Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, 100050, P. R. China
| | - Yitong Liu
- Department of Periodontics, School of Stomatology, Capital Medical University, Tian Tan Xi Li No.4, Beijing, 100050, P. R. China
- Laboratory of Tissue Regeneration and Immunology, Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, 100050, P. R. China
| | - Nannan Han
- Department of Periodontics, School of Stomatology, Capital Medical University, Tian Tan Xi Li No.4, Beijing, 100050, P. R. China
- Laboratory of Tissue Regeneration and Immunology, Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, 100050, P. R. China
| | - Junji Xu
- Department of Periodontics, School of Stomatology, Capital Medical University, Tian Tan Xi Li No.4, Beijing, 100050, P. R. China
- Laboratory of Tissue Regeneration and Immunology, Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, 100050, P. R. China
| | - Yi Liu
- Department of Periodontics, School of Stomatology, Capital Medical University, Tian Tan Xi Li No.4, Beijing, 100050, P. R. China
- Laboratory of Tissue Regeneration and Immunology, Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, 100050, P. R. China
| | - Song Li
- Department of Orthodontics, School of Stomatology, Capital Medical University, Tian Tan Xi Li No.4, Beijing, 100050, P. R. China.
| | - Lijia Guo
- Department of Orthodontics (WangFuJing Campus), School of Stomatology, Capital Medical University, Scylla alley No.11, Beijing, 100006, P. R. China.
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Meseguer-Donlo J, Soldado-Folgado J, Du J, González-Mena A, Blasco-Hernando F, Cañas-Ruano E, Nogués X, Knobel H, Garcia-Giralt N, Güerri-Fernández R. HIV infection is associated with upregulated circulating levels of the inflammaging miR-21-5p. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2023; 56:931-938. [PMID: 37562995 DOI: 10.1016/j.jmii.2023.07.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 06/23/2023] [Accepted: 07/26/2023] [Indexed: 08/12/2023]
Abstract
BACKGROUND HIV infection produces a chronic inflammation which leads to early aging of people living with HIV. Even though antiretroviral treatments (ART) have significantly increased HIV patient survival, an underlying chronic inflammation persists leading to HIV-related comorbidities. In this context, changes in microRNAs (miRNAs) expression may contribute to this inflammatory response. This study aims to detect differential expression of circulating miRNAs in treatment-naïve HIV-infected individuals compared to uninfected controls and evaluation of altered miRNAs after one year of ART. METHODS Serum from patients and controls was collected at baseline and after 48-weeks on ART in HIV-treated patients. Circulating miRNAs were analysed using next generation sequencing. RESULTS A total of 32 HIV patients and 10 controls were recruited. Of HIV+ individuals, 7 were long-term non-progressors (elite controllers), a group of HIV-infected individuals that spontaneously control the infection. Higher circulating levels of miR-21-5p, and lower levels of miR-6503-3p and miR-3135b were detected in HIV+ progressors. After one year of ART, these miRNAs remain altered. Moreover, miR-21-5p and miR-6503-3p were also altered in elite controllers compared to control group. In silico analyses showed that miR-21-5p target pathways are related to inflammation mechanisms and immune system. CONCLUSION miR-21-5p circulating levels are involved in inflammation and oxidative stress mechanisms in HIV patients even after one year of ART or in elite controllers.
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Affiliation(s)
- Javier Meseguer-Donlo
- Universitat Autònoma de Barcelona, Barcelona, Spain; Department of Medicine and Life Sciences (MELIS), Universitat Pompeu Fabra, Barcelona, Spain
| | - Jade Soldado-Folgado
- Universitat Autònoma de Barcelona, Barcelona, Spain; Department of Internal Medicine, Hospital del Mar, Barcelona, Spain
| | - Juan Du
- IMIM (Hospital del Mar Research Institute), Parc de Salut Mar, Department of Infectious Diseases, Barcelona, Spain
| | - Alicia González-Mena
- IMIM (Hospital del Mar Research Institute), Parc de Salut Mar, Department of Infectious Diseases, Barcelona, Spain
| | - Fabiola Blasco-Hernando
- IMIM (Hospital del Mar Research Institute), Parc de Salut Mar, Department of Infectious Diseases, Barcelona, Spain
| | - Esperanza Cañas-Ruano
- IMIM (Hospital del Mar Research Institute), Parc de Salut Mar, Department of Infectious Diseases, Barcelona, Spain
| | - Xavier Nogués
- Department of Internal Medicine, Hospital del Mar, Barcelona, Spain; IMIM (Hospital del Mar Research Institute), Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), ISCIII, Barcelona, Spain
| | - Hernando Knobel
- IMIM (Hospital del Mar Research Institute), Parc de Salut Mar, Department of Infectious Diseases, Barcelona, Spain
| | - Natalia Garcia-Giralt
- IMIM (Hospital del Mar Research Institute), Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), ISCIII, Barcelona, Spain.
| | - Robert Güerri-Fernández
- Universitat Autònoma de Barcelona, Barcelona, Spain; Department of Medicine and Life Sciences (MELIS), Universitat Pompeu Fabra, Barcelona, Spain; IMIM (Hospital del Mar Research Institute), Parc de Salut Mar, Department of Infectious Diseases, Barcelona, Spain; Centro de Investigación Biomédica en Red Enfermedades Infecciosas, CIBERINFEC, Instituto de Salud Carlos III, Madrid, Spain
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Zhao X, Yuan J, Jia J, Zhang J, Liu J, Chen Q, Li T, Wu Z, Wu H, Miao X, Wu T, Li B, Cheng X. Role of non‑coding RNAs in cartilage endplate (Review). Exp Ther Med 2023; 26:312. [PMID: 37273754 PMCID: PMC10236100 DOI: 10.3892/etm.2023.12011] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 04/14/2023] [Indexed: 06/06/2023] Open
Abstract
Cartilage endplate (CEP) degeneration is considered one of the major causes of intervertebral disc degeneration (IDD), which causes non-specific neck and lower back pain. In addition, several non-coding RNAs (ncRNAs), including long ncRNAs, microRNAs and circular RNAs have been shown to be involved in the regulation of various diseases. However, the particular role of ncRNAs in CEP remains unclear. Identifying these ncRNAs and their interactions may prove to be is useful for the understanding of CEP health and disease. These RNA molecules regulate signaling pathways and biological processes that are critical for a healthy CEP. When dysregulated, they can contribute to the development disease. Herein, studies related to ncRNAs interactions and regulatory functions in CEP are reviewed. In addition, a summary of the current knowledge regarding the deregulation of ncRNAs in IDD in relation to their actions on CEP cell functions, including cell proliferation, apoptosis and extracellular matrix synthesis/degradation is presented. The present review provides novel insight into the pathogenesis of IDD and may shed light on future therapeutic approaches.
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Affiliation(s)
- Xiaokun Zhao
- Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Jinghong Yuan
- Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Jingyu Jia
- Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Jian Zhang
- Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Jiahao Liu
- Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Qi Chen
- Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Tao Li
- Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Zhiwen Wu
- Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Hui Wu
- Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Xinxin Miao
- Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Tianlong Wu
- Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
- Jiangxi Key Laboratory of Intervertebral Disc Disease, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Bin Li
- Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
- Jiangxi Key Laboratory of Intervertebral Disc Disease, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Xigao Cheng
- Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
- Jiangxi Key Laboratory of Intervertebral Disc Disease, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
- Institute of Minimally Invasive Orthopedics, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
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Ahmed F, Bappy MNI, Islam MS. Identification of conserved miRNAs and their targets in Jatropha curcas: an in silico approach. J Genet Eng Biotechnol 2023; 21:43. [PMID: 37024763 PMCID: PMC10079790 DOI: 10.1186/s43141-023-00495-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Accepted: 03/18/2023] [Indexed: 04/08/2023]
Abstract
BACKGROUND MicroRNAs (miRNAs) are small endogenous RNAs with an approximate length of 18-22 nucleotides and involved in the regulation of gene expression in transcriptional or post-transcriptional levels. They were found to be associated with leaf morphogenesis, flowering time, vegetative phase change, and response to environmental cues in plants, where they act as a critical regulatory factor. The nature of high conservancy of plant miRNAs within the plant species made it possible to detect the conserved miRNAs by computational approaches. Expressed Sequence Tags (EST) based comparative genomic approaches provide advantages over wet lab approaches as it is convenient, easy to carry out and less time consuming. EST-based in silico approach can unravel new conserved miRNAs in plants, even when the complete genome sequence is not available. RESULTS To identify the novel miRNAs, a total of 46,865 ESTs from Jatropha curcas were searched for homology to all available 6746 mature miRNAs of plant eudicotyledons. Finally, we ended up with 12 novel miRNAs in Jatropha that range from 18 to 19 nucleotides where their respective precursor miRNAs had 54.11-71.76% (A + U) content. The putative miRNAs belong to 12 individual miRNA family and most of them have higher (A + U) content ranging from 47.36 to 77.77% than their respective miRNA homologs. Many of the target genes by the newly identified miRNAs were associated with plant growth and development, stress response, defense and hormone signaling, and oil synthesis pathways. CONCLUSION These findings have the potential to speed up miRNA identification and expand our understanding of miRNA functions in J. curcas.
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Affiliation(s)
- Foeaz Ahmed
- Faculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet, 3100, Bangladesh
- Department of Molecular Biology and Genetic Engineering, Sylhet Agricultural University, Sylhet, 3100, Bangladesh
| | - Md Nazmul Islam Bappy
- Faculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet, 3100, Bangladesh
- Department of Animal and Fish Biotechnology, Sylhet Agricultural University, Sylhet, 3100, Bangladesh
| | - Md Shariful Islam
- Faculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet, 3100, Bangladesh.
- Department of Molecular Biology and Genetic Engineering, Sylhet Agricultural University, Sylhet, 3100, Bangladesh.
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MiRNA-30d and miR-770-5p as potential clinical risk predictors of Vasoplegic Syndrome in Patients undergoing on-pump coronary artery bypass grafting. Sci Rep 2023; 13:2084. [PMID: 36747073 PMCID: PMC9902624 DOI: 10.1038/s41598-023-28978-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Accepted: 01/27/2023] [Indexed: 02/08/2023] Open
Abstract
The aims of this study were to perform pre-surgery miRNA profiling of patients who develop Vasoplegic syndrome (VS) after coronary artery bypass grafting (CABG) and identify those miRNAs that could be used as VS prognostic tools and biomarkers. The levels of 754 microRNAs (miRNAs) were measured in whole blood samples from a cohort of patients collected right before the coronary artery bypass grafting (CABG) surgery. We compared the miRNA levels of those who developed VS (VASO group) with those who did not (NONVASO group) after surgery. Six miRNAs (hsa-miR-548c-3p, -199b-5p, -383-5p -571 -183-3p, -30d-5p) were increased and two (hsa-1236-3p, and hsa-miR770-5p) were decreased in blood of VASO compared to NONVASO groups. Receiver Operating Characteristic (ROC) curve analysis revealed that a combination of the miRNAs, hsa-miR-30d-5p and hsa-miR-770-5p can be used as VS predictors (AUC = 0.9615, p < 0.0001). The computational and functional analyses were performed to gain insights into the potential role of these dysregulated miRNAs in VS and have identified the "Apelin Liver Signaling Pathway" as the canonical pathway containing the most target genes regulated by these miRNAs. The expression of the combined miRNAs hsa-miR-30d and hsa-miR-770-5p allowed the ability to distinguish between patients who could and could not develop VS, representing a potential predictive biomarker of VS.
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Rissanou AN, Karatasos K. Effects of the structure of lipid-based agents in their complexation with a single stranded mRNA fragment: a computational study. SOFT MATTER 2022; 18:6229-6245. [PMID: 35904818 DOI: 10.1039/d2sm00403h] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
In this work we employed fully atomistic molecular dynamics simulations, aiming towards a better understanding of the mechanisms associated with the formation and the stability of lipid-based RNA nanoassemblies, in an aqueous environment. We examined two groups of lipid-based complexation agents, differing in the degree of hydrophobicity and in the overall charge. The first group was comprised of cationic ionizable agents while the second included electrically neutral amphoteric phosphatidylcholine lipids. It was found that the overall charge of the complexation agents played the most decisive role in the energetics of the lipid/RNA association, while their degree of hydrophobicity affected their self-assembly and their complexation kinetics. The latter also affected the structural stability of the formed complexes since the water entrapped within the clusters of the less hydrophobic agents appeared to reduce the coherence of the lipid-RNA nanoassemblies. The combined effects of the aforementioned attributes dictated also the RNA conformation after complexation. The results from the present study provide thus new insight towards controlling the morphology, the energetic stability and the structural integrity of the formed complexes.
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Affiliation(s)
- Anastassia N Rissanou
- Department of Chemical Engineering, University of Thessaloniki, P.O. BOX 420, 54124 Thessaloniki, Greece.
- Department of Mathematics and Applied Mathematics, University of Crete, GR-71409, Heraklion, Crete, Greece.
| | - Kostas Karatasos
- Department of Chemical Engineering, University of Thessaloniki, P.O. BOX 420, 54124 Thessaloniki, Greece.
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Martínez-Gutierrez A, Carbajal-Lopez B, Bui TM, Mendoza-Rodriguez M, Campos-Parra AD, Calderillo-Ruiz G, Cantú-De Leon D, Madrigal-Santillán EO, Sumagin R, Pérez-Plasencia C, Pérez-Yépez EA. A microRNA panel that regulates proinflammatory cytokines as diagnostic and prognosis biomarkers in colon cancer. Biochem Biophys Rep 2022; 30:101252. [PMID: 35313644 PMCID: PMC8933814 DOI: 10.1016/j.bbrep.2022.101252] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 02/23/2022] [Accepted: 03/13/2022] [Indexed: 12/24/2022] Open
Abstract
Colon cancer (CC) is the third most common neoplasm and the fourth cause of cancer-related death worldwide in both sexes. It has been established that inflammation plays a critical role in tumorigenesis and progression of CC. Immune, stromal and tumor cells supply the tumor microenvironment with pro-inflammatory cytokines such as interleukin 1β, TNFα, IL-6 and IL-11, to hyperactivate signaling pathways linked to cancerous processes. Recent findings suggest a putative role of microRNAs (miRNAs) in the progression and management of the inflammatory response in intestinal diseases. Moreover, miRNAs are able to regulate expression of molecular mediators that are linking inflammation and cancer. In this work a miRNA panel differentially expressed between healthy, inflammatory bowel disease (IBD) and CC tissue was established. Identified miRNAs regulate signaling pathways related to inflammation and cancer progression. An inflammation associated-miRNA panel composed of 11-miRNAs was found to be overexpressed in CC but not in inflamed or normal tissues (miR-21-5p, miR-304-5p, miR-577, miR-335-5p, miR-21-3p, miR-27b-5p, miR-335-3p, miR-215-5p, miR-30b-5p, miR-192-5p, miR-3065-5p). The association of top hit miRNAs, miR-3065-5p and miR-30b-5p expression with overall survival of CC patients was demonstrated using Kaplan-Meier tests. Finally, differential miRNA expression was validated using an inflammation-associated CC model induced by Azoxymethane/Dextran Sodium Sulfate (AOM/DSS) to compare miRNA expression in normal and inflamed tissue versus CC tissues. Based on these findings we propose the identified inflammatory miRNA panel as a potent diagnostic tool for CC determination.
A miRNA group distinguishes colon cancer tissues, since early stages, from inflamed or healthy colon tissues. The miRNA panel regulates signaling pathways related to cancer progression. The levels of pro-inflammatory cytokines are regulated by the miRNAs of the panel. Inflammation-related miRNAs are colon cancer prognosis biomarkers. A miRNA signature is specific biomarker for colitis-associated colon carcinogenesis.
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Affiliation(s)
| | - Berenice Carbajal-Lopez
- Laboratorio de Genómica, Instituto Nacional de Cancerología, Tlalpan, Mexico
- Programa de Doctorado en Investigación en Medicina, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico
| | - Triet M. Bui
- Department of Pathology, Northwestern University Feinberg School of Medicine, 300 East Superior St., Chicago, IL, 60611, USA
| | - Monica Mendoza-Rodriguez
- Unidad de Biomedicina, FES-Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, 54090, Mexico
| | | | | | - David Cantú-De Leon
- Unidad de Investigación en Cáncer, Instituto Nacional de Cancerología, Tlalpan, Mexico
| | - Eduardo-Osiris Madrigal-Santillán
- Laboratorio de Medicina de la Conservación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México, 11340, Mexico
| | - Ronen Sumagin
- Department of Pathology, Northwestern University Feinberg School of Medicine, 300 East Superior St., Chicago, IL, 60611, USA
| | - Carlos Pérez-Plasencia
- Laboratorio de Genómica, Instituto Nacional de Cancerología, Tlalpan, Mexico
- Laboratorio de Genómica Funcional. Unidad de Biomedicina, FES-IZTACALA, UNAM, Tlalnepantla, Mexico
- Corresponding author. Laboratorio de Genómica, Instituto Nacional de Cancerología, Tlalpan, Mexico.
| | - Eloy-Andrés Pérez-Yépez
- Laboratorio de Genómica, Instituto Nacional de Cancerología, Tlalpan, Mexico
- Cátedra-CONACYT, Dirección de Cátedras, Consejo Nacional de Ciencia y Tecnología (CONACYT), Mexico
- Corresponding author. Laboratorio de Genómica, Instituto Nacional de Cancerología, Tlalpan, Mexico.
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Li X, Zhou Y, Wen P, Yuan Y, Xiao Z, Shi H, Zhou H. Tumor suppressor LHX6 upregulation contributes to the inhibitory effect of miR-346 knockdown on colorectal cancer cell growth. ENVIRONMENTAL TOXICOLOGY 2022; 37:435-445. [PMID: 34773443 DOI: 10.1002/tox.23410] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 10/04/2021] [Accepted: 11/02/2021] [Indexed: 06/13/2023]
Abstract
Colorectal cancer (CRC) is one of the prevalent types of human malignancies and ranks as the second leading cause of cancer-associated death worldwide. Dysregulated miRNAs have been promulgated as oncogenes or tumor-suppressive genes participating in the initiation and progression of CRC. A recent study reported that miR-346 was highly expressed in CRC patients. However, the biological role and underlying mechanism of miR-346 in CRC remain elusive. qRT-PCR and western blot assays were employed to detect miR-346 and LIM homeobox domain 6 (LHX6) expression in CRC cells. Cell proliferation was evaluated by CCK-8 and BrdU assays. Apoptosis was evaluated by TUNEL assay. The interaction between miR-346 and LHX6 was assessed by luciferase reporter assay. Results showed that miR-346 expression was increased and LHX6 expression was reduced in CRC cells. miR-346 knockdown and LHX6 overexpression inhibited proliferation and promoted apoptosis of CRC cells. Additionally, we found that miR-346 negatively regulated LHX6 expression in CRC cells by directly targeting LHX6. LHX6 knockdown partially attenuated anti-miR-346-induced proliferation reduction and apoptosis promotion in CRC cells. Furthermore, miR-346 knockdown inhibited the protein kinase B (Akt)/mechanistic target of rapamycin (mTOR) pathway in CRC cells by targeting LHX6. The present study indicated that miR-346 knockdown repressed cell growth in CRC cells by upregulating LHX6, and this was associated with inactivation of the Akt/mTOR pathway.
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Affiliation(s)
- Xianzhe Li
- Department of General Surgery, Nanshi Hospital, Nanyang, China
| | - Yeqi Zhou
- Department of Radiotherapy, The Second People's Hospital of Huai'an, Huai'an Hospital Affiliated to Xuzhou Medical University, Huai'an, China
| | - Penghao Wen
- Department of Medical Oncology, Nanshi Hospital, Nanyang, China
| | - Yan Yuan
- Department of Radiotherapy, Nanshi Hospital, Nanyang, China
| | - Zhenghong Xiao
- Department of Medical Oncology, Nanshi Hospital, Nanyang, China
| | - Hengwei Shi
- Department of General Surgery, Nanshi Hospital, Nanyang, China
| | - Hailang Zhou
- Department of Gastroenterology, Lianshui County People's Hospital Affiliated to Kangda College of Nanjing Medical University, Huai'an, China
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11
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The Role of microRNAs in the Mammary Gland Development, Health, and Function of Cattle, Goats, and Sheep. Noncoding RNA 2021; 7:ncrna7040078. [PMID: 34940759 PMCID: PMC8708473 DOI: 10.3390/ncrna7040078] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 12/07/2021] [Accepted: 12/10/2021] [Indexed: 02/07/2023] Open
Abstract
Milk is an integral and therefore complex structural element of mammalian nutrition. Therefore, it is simple to conclude that lactation, the process of producing milk, is as complex as the mammary gland, the organ responsible for this biochemical activity. Nutrition, genetics, epigenetics, disease pathogens, climatic conditions, and other environmental variables all impact breast productivity. In the last decade, the number of studies devoted to epigenetics has increased dramatically. Reports are increasingly describing the direct participation of microRNAs (miRNAs), small noncoding RNAs that regulate gene expression post-transcriptionally, in the regulation of mammary gland development and function. This paper presents a summary of the current state of knowledge about the roles of miRNAs in mammary gland development, health, and functions, particularly during lactation. The significance of miRNAs in signaling pathways, cellular proliferation, and the lipid metabolism in agricultural ruminants, which are crucial in light of their role in the nutrition of humans as consumers of dairy products, is discussed.
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Lisboa PC, Miranda RA, Souza LL, Moura EG. Can breastfeeding affect the rest of our life? Neuropharmacology 2021; 200:108821. [PMID: 34610290 DOI: 10.1016/j.neuropharm.2021.108821] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Revised: 08/17/2021] [Accepted: 09/30/2021] [Indexed: 12/31/2022]
Abstract
The breastfeeding period is one of the most important critical windows in our development, since milk, our first food after birth, contains several compounds, such as macronutrients, micronutrients, antibodies, growth factors and hormones that benefit human health. Indeed, nutritional, and environmental alterations during lactation, change the composition of breast milk and induce alterations in the child's development, such as obesity, leading to the metabolic dysfunctions, cardiovascular diseases and neurobehavioral disorders. This review is based on experimental animal models, most of them in rodents, and summarizes the impact of an adequate breast milk supply in view of the developmental origins of health and disease (DOHaD) concept, which has been proposed by researchers in the areas of epidemiology and basic science from around the world. Here, experimental advances in understanding the programming during breastfeeding were compiled with the purpose of generating knowledge about the genesis of chronic noncommunicable diseases and to guide the development of public policies to deal with and prevent the problems arising from this phenomenon. This review article is part of the special issue on "Cross talk between periphery and brain".
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Affiliation(s)
- Patricia C Lisboa
- Laboratory of Endocrine Physiology, Department of Physiological Sciences, Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
| | - Rosiane A Miranda
- Laboratory of Endocrine Physiology, Department of Physiological Sciences, Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
| | - Luana L Souza
- Laboratory of Endocrine Physiology, Department of Physiological Sciences, Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
| | - Egberto G Moura
- Laboratory of Endocrine Physiology, Department of Physiological Sciences, Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
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Arslan B, İncili ÇY, Ulu F, Horuz E, Bayarslan AU, Öçal M, Kalyoncuoğlu E, Baloglu MC, Altunoglu YC. Comparative genomic analysis of expansin superfamily gene members in zucchini and cucumber and their expression profiles under different abiotic stresses. PHYSIOLOGY AND MOLECULAR BIOLOGY OF PLANTS : AN INTERNATIONAL JOURNAL OF FUNCTIONAL PLANT BIOLOGY 2021; 27:2739-2756. [PMID: 35035133 PMCID: PMC8720134 DOI: 10.1007/s12298-021-01108-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Revised: 11/17/2021] [Accepted: 11/25/2021] [Indexed: 05/25/2023]
Abstract
UNLABELLED Zucchini and cucumber belong to the Cucurbitaceae family, a group of economical and nutritious food plants that is consumed worldwide. Expansin superfamily proteins are generally localized in the cell wall of plants and are known to possess an effect on cell wall modification by causing the expansion of this region. Although the whole genome sequences of cucumber and zucchini plants have been resolved, the determination and characterization of expansin superfamily members in these plants using whole genomic data have not been implemented yet. In the current study, a genome-wide analysis of zucchini (Cucurbita pepo) and cucumber (Cucumis sativus) genomes was performed to determine the expansin superfamily genes. In total, 49 and 41 expansin genes were identified in zucchini and cucumber genomes, respectively. All expansin superfamily members were subjected to further bioinformatics analysis including gene and protein structure, ontology of the proteins, phylogenetic relations and conserved motifs, orthologous relations with other plants, targeting miRNAs of those genes and in silico gene expression profiles. In addition, various abiotic stress responses of zucchini and cucumber expansin genes were examined to determine their roles in stress tolerance. CsEXPB-04 and CsEXPA-11 from cucumber and CpEXPA-20 and CpEXPLA-14 from zucchini can be candidate genes for abiotic stress response and tolerance in addition to their roles in the normal developmental processes, which are supported by the gene expression analysis. This work can provide new perspectives for the roles of expansin superfamily genes and offers comprehensive knowledge for future studies investigating the modes of action of expansin proteins. SUPPLEMENTARY INFORMATION The online version contains supplementary material available at 10.1007/s12298-021-01108-w.
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Affiliation(s)
- Büşra Arslan
- Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Kastamonu University, Kastamonu, Turkey
| | - Çınar Yiğit İncili
- Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Kastamonu University, Kastamonu, Turkey
| | - Ferhat Ulu
- Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Kastamonu University, Kastamonu, Turkey
| | - Erdoğan Horuz
- Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Kastamonu University, Kastamonu, Turkey
| | - Aslı Ugurlu Bayarslan
- Department of Biology, Faculty of Science and Arts, Kastamonu University, Kastamonu, Turkey
| | - Mustafa Öçal
- Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Kastamonu University, Kastamonu, Turkey
| | - Elif Kalyoncuoğlu
- Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Kastamonu University, Kastamonu, Turkey
| | - Mehmet Cengiz Baloglu
- Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Kastamonu University, Kastamonu, Turkey
| | - Yasemin Celik Altunoglu
- Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Kastamonu University, Kastamonu, Turkey
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Cen X, Pan X, Zhang B, Huang W, Pei F, Luo T, Huang X, Liu J, Zhao Z. miR-20a-5p contributes to osteogenic differentiation of human dental pulp stem cells by regulating BAMBI and activating the phosphorylation of Smad5 and p38. Stem Cell Res Ther 2021; 12:421. [PMID: 34294156 PMCID: PMC8296686 DOI: 10.1186/s13287-021-02501-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Accepted: 07/04/2021] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Human dental pulp stem cells (hDPSCs) are the preferable choice of seed cells for craniomaxillofacial bone tissue regeneration. As a member of the miR-17-92 cluster, miR-20a-5p functions as an important regulator during bone remodeling. This study aimed to investigate the roles and mechanisms of miR-20a-5p during osteogenesis of hDPSCs. METHODS Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was conducted to determine the expression of miR-20a-5p during osteogenesis of hDPSCs. We interfered with the expression of miR-20a-5p in hDPSCs to clarify the function of miR-20a-5p on osteogenesis both in vitro and vivo. Direct bind sites between miR-20a-5p and BAMBI were confirmed by dual-luciferase reporter assay, and the underlying mechanisms were investigated with cell co-transfections. RESULTS The expression of miR-20a-5p was showed to be upregulated during osteogenesis of hDPSCs. Inhibition of miR-20a-5p could weaken the intensity of ALP/ARS staining and downregulate the expression of mRNAs and proteins of osteogenic markers, while overexpression of miR-20a-5p could enhance the intensity of ALP/ARS staining and the expression of osteogenic markers. Both micro-CT reconstruction images and histological results showed that miR-20a-5p could promote the regeneration of calvarial defects. miR-20a-5p directly targeted bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI), and the latter one was an inhibitor of hDPSC osteogenesis. Silencing BAMBI partially reversed the suppression effect of miR-20a-5p knockdown on osteogenesis. Phosphorylation of Smad5 and p38 was decreased when miR-20a-5p was silenced, whereas p-Smad5 and p-p38 were upregulated when miR-20a-5p was overexpressed or BAMBI was silenced. CONCLUSIONS It is demonstrated that miR-20a-5p functioned as a regulator of BAMBI to activate the phosphorylation of Smad5 and p38 during osteogenic differentiation of hDPSCs.
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Affiliation(s)
- Xiao Cen
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, 3rd Section, South Renmin Road, Chengdu, 610041, Sichuan, China
- Department of Temporomandibular Joint, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Xuefeng Pan
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, 3rd Section, South Renmin Road, Chengdu, 610041, Sichuan, China
- Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Bo Zhang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, 3rd Section, South Renmin Road, Chengdu, 610041, Sichuan, China
- Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Wei Huang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, 3rd Section, South Renmin Road, Chengdu, 610041, Sichuan, China
- Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Fang Pei
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, 3rd Section, South Renmin Road, Chengdu, 610041, Sichuan, China
- Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Tao Luo
- Department of Stomatology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Xinqi Huang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, 3rd Section, South Renmin Road, Chengdu, 610041, Sichuan, China.
- Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
| | - Jun Liu
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, 3rd Section, South Renmin Road, Chengdu, 610041, Sichuan, China
- Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Zhihe Zhao
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, 3rd Section, South Renmin Road, Chengdu, 610041, Sichuan, China
- Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
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15
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Xiang P, Yeung YT, Wang J, Wu Q, Du R, Huang C, Jia X, Gao Y, Zhi Y, Guo F, Wei H, Zhang D, Liu Y, Liu L, Liang L, Wang J, Song Y, Liu K, Fang B. miR-17-3p promotes the proliferation of multiple myeloma cells by downregulating P21 expression through LMLN inhibition. Int J Cancer 2021; 148:3071-3085. [PMID: 33609405 PMCID: PMC8248421 DOI: 10.1002/ijc.33528] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Revised: 01/31/2021] [Accepted: 02/11/2021] [Indexed: 01/01/2023]
Abstract
Multiple myeloma (MM), a hematological malignancy, has a poor prognosis and requires an invasive procedure. Reports have implicated miRNAs in the diagnosis, treatment and prognosis of hematological malignancies. In our study, we evaluated the expression profiles of miR-17-3p in plasma and bone marrow mononuclear cells of monoclonal gammopathy of undetermined significance (MGUS) and MM patients and healthy subjects. The results showed that the plasma and mononuclear cell expression levels of miR-17-3p in MM patients were higher than those in MGUS patients and normal controls. In addition, the expression of miR-17-3p was positively correlated with diagnostic indexes, such as marrow plasma cell abundance and serum M protein level, and positively correlated with the International Staging System stage of the disease. Receiver operating characteristic curve analysis suggested that miR-17-3p might be a diagnostic index of MM. Moreover, miR-17-3p regulated cell proliferation, apoptosis and the cell cycle through P21 in MM cell lines and promoted MM tumor growth in vivo. Furthermore, we predicted and verified LMLN as a functional downstream target gene of miR-17-3p. Negatively regulated by miR-17-3p, LMLN inhibits MM cell growth, exerting a tumor suppressive function through P21. Taken together, our data identify miR-17-3p as a promising diagnostic biomarker for MM in the clinic and unveil a new miR-17-3p-LMLN-P21 axis in MM progression.
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Affiliation(s)
- Pu Xiang
- Department of HematologyAffiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Henan Hematology InstituteZhengzhouHenanChina
| | - Yiu To Yeung
- China‐US (Henan) Hormel Cancer InstituteZhengzhouHenanChina
| | - Jiheng Wang
- Department of Head and Neck ThyroidAffiliated Cancer Hospital of Zhengzhou University and Henan Cancer HospitalZhengzhouHenanChina
| | - Qiong Wu
- China‐US (Henan) Hormel Cancer InstituteZhengzhouHenanChina
- Department of Pathophysiology, School of Basic Medical SciencesZhengzhou UniversityZhengzhouHenanChina
| | - Ruijuan Du
- China‐US (Henan) Hormel Cancer InstituteZhengzhouHenanChina
- Department of Pathophysiology, School of Basic Medical SciencesZhengzhou UniversityZhengzhouHenanChina
| | - Chuntian Huang
- China‐US (Henan) Hormel Cancer InstituteZhengzhouHenanChina
- Department of Pathophysiology, School of Basic Medical SciencesZhengzhou UniversityZhengzhouHenanChina
| | - Xuechao Jia
- China‐US (Henan) Hormel Cancer InstituteZhengzhouHenanChina
- Department of Pathophysiology, School of Basic Medical SciencesZhengzhou UniversityZhengzhouHenanChina
| | - Yunfeng Gao
- China‐US (Henan) Hormel Cancer InstituteZhengzhouHenanChina
| | - Yafei Zhi
- China‐US (Henan) Hormel Cancer InstituteZhengzhouHenanChina
- Department of Pathophysiology, School of Basic Medical SciencesZhengzhou UniversityZhengzhouHenanChina
| | - Fangqin Guo
- Department of Pathophysiology, School of Basic Medical SciencesZhengzhou UniversityZhengzhouHenanChina
| | - Huifang Wei
- China‐US (Henan) Hormel Cancer InstituteZhengzhouHenanChina
- Department of Pathophysiology, School of Basic Medical SciencesZhengzhou UniversityZhengzhouHenanChina
| | - Dandan Zhang
- China‐US (Henan) Hormel Cancer InstituteZhengzhouHenanChina
| | - Yuzhang Liu
- Department of HematologyAffiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Henan Hematology InstituteZhengzhouHenanChina
| | - Lina Liu
- Department of HematologyAffiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Henan Hematology InstituteZhengzhouHenanChina
| | - Lijie Liang
- Department of HematologyAffiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Henan Hematology InstituteZhengzhouHenanChina
| | - Juan Wang
- Department of HematologyAffiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Henan Hematology InstituteZhengzhouHenanChina
| | - Yongping Song
- Department of HematologyAffiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Henan Hematology InstituteZhengzhouHenanChina
| | - Kangdong Liu
- China‐US (Henan) Hormel Cancer InstituteZhengzhouHenanChina
- Department of Pathophysiology, School of Basic Medical SciencesZhengzhou UniversityZhengzhouHenanChina
- Cancer Chemoprevention International Collaboration LaboratoryZhengzhouHenanChina
| | - Baijun Fang
- Department of HematologyAffiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Henan Hematology InstituteZhengzhouHenanChina
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16
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Tong SJ, Zhang XY, Guo HF, Yang J, Qi YP, Lu S. Study on effects of miR-141-3p in proliferation, migration, invasion and apoptosis of colon cancer cells by inhibiting Bcl2. Clin Transl Oncol 2021; 23:2526-2535. [PMID: 34086253 DOI: 10.1007/s12094-021-02653-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Accepted: 05/24/2021] [Indexed: 11/27/2022]
Abstract
PURPOSE This study aimed to investigate the relationship between miR-141-3p and B lymphocyte-2 gene (Bcl2) gene and its biological behavior on colon cancer cell line SW480. METHODS qRT-PCR was used to detect the expression level of miR-141-3p in colon cancer tissues and adjacent tissues, as well as in colon cancer cell line and normal human colonic epithelial cell line FHC. MTT assay, wound assay, and Transwell demonstrated the effects of miR-141-3p on colon cancer proliferation, migration and invasion. Targetscan7.1 predictive software and dual luciferase reporter assays were used to detect the targeted regulation of miR-141-3p on the apoptosis-related gene Bcl2. MTT assay, wound assay, Transwell and flow cytometry were used to detect the effect of Bcl2 on miR-141-3p on colon cancer proliferation, migration, invasion and apoptosis. RESULTS Compared with adjacent tissues, the expression of miR-141-3p in colon cancer tissues was significantly down-regulated. Colon cancer patients with low expression of miR-141-3p had poorer prognosis. Compared with normal colonic epithelial cells, miR-141-3p expression was significantly down-regulated in colon cancer cell lines, and overexpression of miR-141-3p significantly attenuated the proliferation, migration and invasion of colon cancer cells. Knockdown of miR-141-3p significantly promoted the proliferation, migration and invasion of colon cancer cells. miR-141-3p targets the negative regulation of Bcl2. Knockdown of Bcl2 significantly attenuated the promotion of miR-141-3p inhibitor on proliferation, migration and invasion of colon cancer cells and inhibition of apoptosis. Knockdown of Bcl2 significantly enhanced the inhibition effect of miR-141-3p inhibitor on proliferation, migration and invasion of colon cancer cells. CONCLUSIONS In conclusion, miR-141-3p can inhibit the cancer by regulating Bcl2, and miR-141-3p has the potential to become a potential therapeutic target for colon cancer.
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Affiliation(s)
- S J Tong
- Ward 1, Department of General Surgery, The Third Affiliated Hospital of Qiqihaer Medical University, No. 27 Taishun Street, Tiefeng District, Qiqihaer City, 161000, Heilongjiang Province, China
| | - X Y Zhang
- Department of Stomatology, The Third Affiliated Hospital of Qiqihaer Medical University, Qiqihaer City, 161000, China
| | - H F Guo
- Ward 1, Department of General Surgery, The Third Affiliated Hospital of Qiqihaer Medical University, No. 27 Taishun Street, Tiefeng District, Qiqihaer City, 161000, Heilongjiang Province, China
| | - J Yang
- Ward 1, Department of General Surgery, The Third Affiliated Hospital of Qiqihaer Medical University, No. 27 Taishun Street, Tiefeng District, Qiqihaer City, 161000, Heilongjiang Province, China
| | - Y P Qi
- Ward 1, Department of General Surgery, The Third Affiliated Hospital of Qiqihaer Medical University, No. 27 Taishun Street, Tiefeng District, Qiqihaer City, 161000, Heilongjiang Province, China
| | - S Lu
- Ward 1, Department of General Surgery, The Third Affiliated Hospital of Qiqihaer Medical University, No. 27 Taishun Street, Tiefeng District, Qiqihaer City, 161000, Heilongjiang Province, China.
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17
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Sun X, Hou L, Qiu C, Kong B. MiR-501 promotes tumor proliferation and metastasis by targeting HOXD10 in endometrial cancer. Cell Mol Biol Lett 2021; 26:20. [PMID: 34022794 PMCID: PMC8141179 DOI: 10.1186/s11658-021-00268-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 05/19/2021] [Indexed: 02/08/2023] Open
Abstract
Background Several studies have shown the crucial role of miR-501 in regulating cellular pathology in various cancers. However, the function and expression of miR-501 in endometrial cancer (EC) remain obscure.
Methods The expression of miR-501 was determined using quantitative real-time PCR. MTT assay, colony formation assay and cell cycle analysis were used to evaluate the proliferation ability. Migration and invasion were assessed using transwell assay. Tumor formation in nude mice was used to observe the effects of miR-501 on cell proliferation and migration in vivo. Luciferase assay, quantitative real-time PCR and western blot were applied to determine that HOXD10 was the target gene of miR-501. Results In this study, we observed significantly up-regulated expression of miR-501 in endometrial cancer, which correlated with higher pelvic lymph node metastasis and shorter overall survival in high-grade endometrial cancer. High expression of miR-501 was also found in the copy-number-high group than other groups. Moreover, in vitro and in vivo assay showed that overexpression of miR-501 can promote proliferation and metastasis. Mechanistically, we found that miR-501 promotes tumor progression by directly targeting HOXD10. Further study also indicated that miR-501 overexpression can activate the AKT/mTOR pathway. Conclusions MiR-501, which functions as an oncomir in endometrial cancer, might be a potential therapeutic target in high grade endometrial cancer. Supplementary Information The online version contains supplementary material available at 10.1186/s11658-021-00268-7.
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Affiliation(s)
- Xiaomei Sun
- Department of Obstetrics and Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, People's Republic of China.,Key Laboratory of Gynecologic Oncology of Shandong Province, Qilu Hospital of Shandong University, Jinan, People's Republic of China
| | - Lingtong Hou
- Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Chunping Qiu
- Key Laboratory of Gynecologic Oncology of Shandong Province, Qilu Hospital of Shandong University, Jinan, People's Republic of China.,Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China
| | - Beihua Kong
- Key Laboratory of Gynecologic Oncology of Shandong Province, Qilu Hospital of Shandong University, Jinan, People's Republic of China. .,Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.
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18
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Xie Z, Rahman I, Goniewicz ML, Li D. Perspectives on Epigenetics Alterations Associated with Smoking and Vaping. FUNCTION (OXFORD, ENGLAND) 2021; 2:zqab022. [PMID: 35330676 PMCID: PMC8788872 DOI: 10.1093/function/zqab022] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 04/03/2021] [Accepted: 04/21/2021] [Indexed: 01/11/2023]
Abstract
Epigenetic alterations, including DNA methylation, microRNA, and long noncoding RNA, play important roles in the pathogenesis of numerous respiratory health conditions and diseases. Exposure to tobacco smoking has been found to be associated with epigenetic changes in the respiratory tract. Marketed as a less harmful alternative to combustible cigarettes, electronic cigarette (e-cigarette) has rapidly gained popularity in recent years, especially among youth and young adults. Accumulative evidence from both animal and human studies has shown that e-cigarette use (vaping) is also linked to similar respiratory health conditions as observed with cigarette smoking, including wheezing, asthma, and COPD. This review aims to provide an overview of current studies on associations of smoking and vaping with epigenetic alterations in respiratory cells and provide future research directions in epigenetic studies related to vaping.
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Affiliation(s)
- Zidian Xie
- Department of Clinical & Translational Research, University of Rochester Medical Center, Rochester, NY, USA
| | - Irfan Rahman
- Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY, USA
| | - Maciej L Goniewicz
- Department of Health Behavior, Roswell Park Comprehensive Cancer Center, Elm and Carlton Streets, Buffalo, NY, USA
| | - Dongmei Li
- Department of Clinical & Translational Research, University of Rochester Medical Center, Rochester, NY, USA,Address correspondence to D.L. (e-mail: )
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Genome-Wide Identification and Analysis of Nilaparvata lugens microRNAs during Challenge with the Entomopathogenic Fungus Metarhizium anisopliae. J Fungi (Basel) 2021; 7:jof7040295. [PMID: 33919937 PMCID: PMC8070897 DOI: 10.3390/jof7040295] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 04/08/2021] [Accepted: 04/13/2021] [Indexed: 12/11/2022] Open
Abstract
The resistance of the notorious rice pest Nilaparvata lugens to many insecticides has caused significant concerns. Our previous study demonstrated that the fungus Metarhizium anisopliae CQMa421 shows great potential for the control of this pest, but the interactions between them are still unclear. Thus, we further investigated fungal infection-related microRNAs (miRNAs) in N. lugens during M. anisopliae CQMa421 challenge using Illumina sequencing. In this study, we constructed twenty-four small RNA libraries over different time courses (i.e., 4 h, 8 h, 16 h, and 24 h). A total of 478.62 M clean reads were collected, with each sample producing more than 13.37 M reads, after the removal of low-quality reads. We identified 2324 miRNAs and their 11,076 target genes within the twenty-four libraries by bioinformatics analysis. Differentially expressed miRNAs (DEmiRNAs), including 58 (32 upregulated vs. 26 downregulated), 62 (30 upregulated vs. 32 downregulated), 126 (71 upregulated vs. 55 downregulated), and 109 (40 upregulated vs. 69 downregulated) DEmiRNAs were identified at 4 h, 8 h, 16 h, and 24 h post-infection, respectively. We further conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to predict the functions of all target genes of DEmiRNAs. These DEmiRNAs targets identified during 24 h of infection were primarily involved in energy metabolism, lysine degradation, the FoxO signaling pathway, ubiquitin-mediated proteolysis, the mRNA surveillance pathway, and the MAPK signaling pathway. Taken together, our results provide essential information for further study of the interactions between the entomopathogenic fungus M. anisopliae and N. lugens at the posttranscriptional level.
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20
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Transcriptome Analysis of the Chicken Follicular Theca Cells with miR-135a-5p Suppressed. G3-GENES GENOMES GENETICS 2020; 10:4071-4081. [PMID: 32900904 PMCID: PMC7642930 DOI: 10.1534/g3.120.401701] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
As a class of transcription regulators, numerous miRNAs have been verified to participate in regulating ovary follicular development in chickens (Gallus gallus). Previously we showed that gga-miR-135a-5p has significant differential expression between high and low-yield chicken ovaries, and the abundance of gga-miR-135a-5p is significantly higher in follicular theca cells than in granulosa cells. However, the exact role of gga-miR-135a-5p in chicken follicular theca cells is unclear. In this study, primary chicken follicular theca cells were isolated and then transfected with gga-miR-135a-5p inhibitor. Transcriptome sequencing was performed in chicken follicular theca cells with or without transfection. Differentially expressed genes (DEGs) were analyzed using bioinformatics. A dual-luciferase reporter assay was used to verify the target relationship between gga-miR-135a-5p and predicted targets within the DEGs. Compared with the normal chicken follicle theca cells, 953 up-regulated and 1060 down-regulated genes were detected in cells with gga-miR-135a-5p inhibited. The up-regulated genes were significantly enriched in Gene Ontology terms and pathways involved in cell proliferation and differentiation. In chicken follicular theca cells, Krüppel-like factor 4 (KLF4), ATPase phospholipid transporting 8A1 (ATP8A1), and Complexin-1 (CPLX1) were significantly up-regulated when the expression of gga-miR-135a-5p was inhibited. In addition, KLF4, ATP8A1, and CPLX1 confirmed as targets of gga-miR-135a-5p by using a dual-luciferase assay in vitro. The results suggest that gga-mir-135a-5p may involve in proliferation and differentiation in chicken ovarian follicular theca cells by targeting KLF4, ATP8A1, and CPLX1.
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21
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Hemmat N, Bannazadeh Baghi H. Association of human papillomavirus infection and inflammation in cervical cancer. Pathog Dis 2020; 77:5558235. [PMID: 31504464 DOI: 10.1093/femspd/ftz048] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Accepted: 09/01/2019] [Indexed: 12/11/2022] Open
Abstract
Human papillomavirus (HPV) associated cancers, and in particular cervical cancer, are considered to be directly stimulated by HPV oncogenes. Alternatively, these types of cancers could also be indirectly stimulated by HPV-induced chronic inflammations, which in turn are also caused by HPV oncogenes activity. Chronic inflammation is associated with repeated tissue injury and development of mutations in the vital tumor suppressor genes. Thus, it is important to understand that the persistent HPV infection and its associated chronic inflammation is responsible for the progression of HPV-induced cancers. HPV E5, E6 and E7 could upregulate the expression of cyclooxygenase (COX)-2 and prostaglandin (PG) E2 followed by the activation of the COX-PG pathway. This pathway is assumed to be the main cause of HPV-induced inflammation. Additionally, HPV oncogenes could have an impact on the upregulation of pro-inflammatory cytokines in HPV-positive patients. The upregulation of such cytokines accelerates the incidence of inflammation following HPV infection. Other factors such as microRNAs, which are involved in the inflammation pathways and aging, give rise to the increased level of pro-inflammatory cytokines and could also be responsible for the acceleration of HPV-induced inflammation and consequent cervical cancer. In this review, the exact roles of HPV oncogenes in the occurrence of inflammation in cervical tissue, and the effects of other factors in this event are evaluated.
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Affiliation(s)
- Nima Hemmat
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Drug Applied Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hossein Bannazadeh Baghi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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22
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Xin H, Wang C, Chi Y, Liu Z. MicroRNA-196b-5p promotes malignant progression of colorectal cancer by targeting ING5. Cancer Cell Int 2020; 20:119. [PMID: 32308564 PMCID: PMC7149860 DOI: 10.1186/s12935-020-01200-3] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2019] [Accepted: 03/31/2020] [Indexed: 12/21/2022] Open
Abstract
Background miR-196b-5p expression is deregulated in many malignant tumors. Although miR-196b-5p has been implicated in the malignant transformation of colorectal cancer, its role in this specific type of cancer has not been fully explored. Thus, the present study was aimed to examine the cellular function of miR-196b-5p and its role in malignant biological behavior in colorectal cancer. Methods miR-196b-5p expression was measured in colorectal cancer tissues and cell lines using quantitative real-time PCR. Cell counting kit-8 (CCK-8) assay and Transwell assay were used to detect proliferation, migration, and invasion in cell lines, whereas flow cytometry was applied to study apoptosis. Western blot analysis was performed to measure the protein levels. Dual luciferase reporter assay was used to investigate the interaction between miR-196b-5p and ING5. Tumor formation was evaluated in mice. Results MiR-196b-5p was abundantly expressed in colorectal cancer tissues and cell lines, whereas ING5 was expressed at low levels. MiR-196b-5p was successfully overexpressed or knocked down in colorectal cancer cells. We found that miR-196b-5p overexpression significantly accelerated the proliferation, cell cycle, migration and invasion, while inhibited cell apoptosis in colorectal cancer cells. However, miR-196b-5p inhibitor showed the opposite effects. Moreover, ING5 overexpression or knockdown was successfully performed in colorectal cancer cells. ING5 overexpression suppressed proliferation, migration, invasion, the phosphorylation of PI3K, Akt as well as MEK, and promoted cell apoptosis, which could be reversed by ING5 knockdown. Additionally, ING5 was identified as a target of miR-196b-5p through bioinformatics analysis and a luciferase activity assay. Furthermore, ING5 knockdown could attenuate the decrease in proliferation, migration, invasion, and the protein levels of p-PI3K, p-Akt, and p-MEK, which were induced by miRNA-196b-5p inhibitor. Besides, miR-196b-5p knockdown inhibited tumor growth, whereas ING5 knockdown elevated it in vivo. Conclusions In conclusion, miR-196b-5p promotes cell proliferation, migration, invasion, and inhibits apoptosis in colorectal cancer by targeting ING5.
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Affiliation(s)
- He Xin
- Department of Radiology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004 People's Republic of China
| | - Chuanzhuo Wang
- Department of Radiology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004 People's Republic of China
| | - Yuan Chi
- Department of Radiology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004 People's Republic of China
| | - Zhaoyu Liu
- Department of Radiology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004 People's Republic of China
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23
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Zhu Y, Li K, Yan L, He Y, Wang L, Sheng L. miR-223-3p promotes cell proliferation and invasion by targeting Arid1a in gastric cancer. Acta Biochim Biophys Sin (Shanghai) 2020; 52:150-159. [PMID: 31912865 DOI: 10.1093/abbs/gmz151] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Revised: 11/18/2019] [Accepted: 11/28/2019] [Indexed: 12/24/2022] Open
Abstract
Accumulating evidence has indicated that microRNAs can regulate downstream signaling pathways and play an important role in various tumors. In this study, we found that miR-223-3p was differentially expressed in 40 paired gastric cancer tissues and adjacent tissues and that miR-223-3p was positively correlated with tumor invasion depth and lymph node metastasis. Luciferase reporter assay confirmed that Arid1a was the target gene of miR-223-3p. Functional assays showed that miR-223-3p promoted the proliferation and invasion of gastric cancer cells by regulating the expression of Arid1a. We also confirmed that miR-223-3p regulated the growth of gastric cancer cells in vivo, while an antagomir against miR-223-3p significantly inhibited tumor growth. In conclusion, our results demonstrated that miR-223-3p inhibits gastric cancer cell progression by decreasing the expression of Arid1a. Therefore, miR-223-3p may act as a potential therapeutic target for patients with gastric cancer.
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Affiliation(s)
- Yiping Zhu
- Department of Oncology, The First Affiliated Hospital of Wannan Medical College, Wuhu 241000, China
| | - Kai Li
- School of Graduate Studies, Wannan Medical College, Wuhu 241000, China
- Provincial Key Laboratory of Biological Macro-molecules Research, Wannan Medical College, Wuhu 241000, China
| | - Liang Yan
- Provincial Key Laboratory of Biological Macro-molecules Research, Wannan Medical College, Wuhu 241000, China
| | - Yang He
- Department of Oncology, The First Affiliated Hospital of Wannan Medical College, Wuhu 241000, China
| | - Lu Wang
- Department of Oncology, The First Affiliated Hospital of Wannan Medical College, Wuhu 241000, China
| | - Lili Sheng
- Department of Oncology, The First Affiliated Hospital of Wannan Medical College, Wuhu 241000, China
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24
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He Z, Dang J, Song A, Cui X, Ma Z, Zhang Y. The involvement of miR-150/β-catenin axis in colorectal cancer progression. Biomed Pharmacother 2020; 121:109495. [DOI: 10.1016/j.biopha.2019.109495] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 09/17/2019] [Accepted: 09/26/2019] [Indexed: 10/25/2022] Open
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25
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Daoud AZ, Mulholland EJ, Cole G, McCarthy HO. MicroRNAs in Pancreatic Cancer: biomarkers, prognostic, and therapeutic modulators. BMC Cancer 2019; 19:1130. [PMID: 31752758 PMCID: PMC6868851 DOI: 10.1186/s12885-019-6284-y] [Citation(s) in RCA: 156] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Accepted: 10/24/2019] [Indexed: 02/06/2023] Open
Abstract
A severe lack of early diagnosis coupled with resistance to most available therapeutic options renders pancreatic cancer as a major clinical concern. The limited efficacy of current treatments necessitates the development of novel therapeutic strategies that are based on an understanding of the molecular mechanisms involved in pancreatic cancer progression. MicroRNAs (miRNAs) are non-coding small RNAs that regulate the expression of multiple proteins in the post-translation process and thus have promise as biomarkers, prognostic agents, and as advanced pancreatic therapies. Profiling of deregulated miRNAs in pancreatic cancer can correlate to diagnosis, indicate optimal treatment and predict response to therapy. Furthermore, understanding the main effector genes in pancreatic cancer along with downstream pathways can identify possible miRNAs as therapeutic candidates. Additionally, obstacles to the translation of miRNAs into the clinic are also considered. Distinct miRNA expression profiles can correlate to stages of malignant pancreatic disease, and hold potential as biomarkers, prognostic markers and clinical targets. However, a limited understanding and validation of the specific role of such miRNAs stunts clinical application. Target prediction using algorithms provides a wide range of possible targets, but these miRNAs still require validation through pre-clinical studies to determine the knock-on genetic effects.
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Affiliation(s)
- Afra Z Daoud
- School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Northern Ireland, BT9 7BL, UK
| | - Eoghan J Mulholland
- Gastrointestinal Stem Cell Biology Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK
| | - Grace Cole
- Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, British Columbia, V5Z 1L3, Canada
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, V6T 2B5, Canada
| | - Helen O McCarthy
- School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Northern Ireland, BT9 7BL, UK.
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26
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Redmond W, Allen D, Elledge MC, Arellanes R, Redmond L, Yeahquo J, Zhang S, Youngblood M, Reiner A, Seo J. Screening of microRNAs controlling body fat in Drosophila melanogaster and identification of miR-969 and its target, Gr47b. PLoS One 2019; 14:e0219707. [PMID: 31318925 PMCID: PMC6638924 DOI: 10.1371/journal.pone.0219707] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Accepted: 06/28/2019] [Indexed: 01/23/2023] Open
Abstract
MicroRNAs (miRNAs) are small non-protein coding RNAs and post-transcriptionally regulate cellular gene expression. In animal development, miRNAs play essential roles such as stem cell maintenance, organogenesis, and apoptosis. Using gain-of-function (GOF) screening with 160 miRNA lines in Drosophila melanogaster, we identified a set of miRNAs which regulates body fat contents and named them microCATs (microRNAs Controlling Adipose Tissue). Further examination of egg-to-adult developmental kinetics of selected miRNA lines showed a negative correlation between fat content and developmental time. Comparison of microCATs with loss-of-function miRNA screening data uncovered miR-969 as an essential regulator of adiposity. Subsequently, we demonstrated adipose tissue-specific knock-down of gustatory receptor 47b (Gr47b), a miR-969 target, greatly reduced the amount of body fat, recapitulating the miR-969 GOF phenotype.
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Affiliation(s)
- William Redmond
- Department of Biology, School of Arts and Sciences, Rogers State University, Claremore, Oklahoma, United States of America
| | - Dylan Allen
- Department of Biology, School of Arts and Sciences, Rogers State University, Claremore, Oklahoma, United States of America
| | - M. Christian Elledge
- Department of Biology, School of Arts and Sciences, Rogers State University, Claremore, Oklahoma, United States of America
| | - Russell Arellanes
- Department of Biology, School of Arts and Sciences, Rogers State University, Claremore, Oklahoma, United States of America
| | - Lucille Redmond
- Department of Biology, School of Arts and Sciences, Rogers State University, Claremore, Oklahoma, United States of America
| | - Jared Yeahquo
- Department of Biology, School of Arts and Sciences, Rogers State University, Claremore, Oklahoma, United States of America
| | - Shuyin Zhang
- Department of Biology, School of Arts and Sciences, Rogers State University, Claremore, Oklahoma, United States of America
| | - Morgan Youngblood
- Department of Biology, School of Arts and Sciences, Rogers State University, Claremore, Oklahoma, United States of America
| | - Austin Reiner
- Department of Biology, School of Arts and Sciences, Rogers State University, Claremore, Oklahoma, United States of America
| | - Jin Seo
- Department of Biology, School of Arts and Sciences, Rogers State University, Claremore, Oklahoma, United States of America
- * E-mail:
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27
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Liu GF, Yang T. Identification of a microRNA switch in spinal commissural axon guidance. Neural Regen Res 2019; 14:1208-1209. [PMID: 30804247 PMCID: PMC6425835 DOI: 10.4103/1673-5374.251300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Affiliation(s)
- Guo-fa Liu
- Department of Biological Sciences, University of Toledo, Toledo, OH, USA,Correspondence to: Guo-fa Liu, .
| | - Tao Yang
- Department of Biological Sciences, University of Toledo, Toledo, OH, USA
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28
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MiR-141–3p inhibits cell proliferation, migration and invasion by targeting TRAF5 in colorectal cancer. Biochem Biophys Res Commun 2019; 514:699-705. [DOI: 10.1016/j.bbrc.2019.05.002] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2019] [Accepted: 05/01/2019] [Indexed: 11/23/2022]
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Factors Regulating microRNA Expression and Function in Multiple Myeloma. Noncoding RNA 2019; 5:ncrna5010009. [PMID: 30654527 PMCID: PMC6468559 DOI: 10.3390/ncrna5010009] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Revised: 01/13/2019] [Accepted: 01/15/2019] [Indexed: 12/15/2022] Open
Abstract
Intensive research has been undertaken during the last decade to identify the implication of microRNAs (miRNAs) in the pathogenesis of multiple myeloma (MM). The expression profiling of miRNAs in MM has provided relevant information, demonstrating different patterns of miRNA expression depending on the genetic abnormalities of MM and a key role of some miRNAs regulating critical genes associated with MM pathogenesis. However, the underlying causes of abnormal expression of miRNAs in myeloma cells remain mainly elusive. The final expression of the mature miRNAs is subject to multiple regulation mechanisms, such as copy number alterations, CpG methylation or transcription factors, together with impairment in miRNA biogenesis and differences in availability of the mRNA target sequence. In this review, we summarize the available knowledge about the factors involved in the regulation of miRNA expression and functionality in MM.
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30
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Nagaraju M, Kumar SA, Reddy PS, Kumar A, Rao DM, Kavi Kishor PB. Genome-scale identification, classification, and tissue specific expression analysis of late embryogenesis abundant (LEA) genes under abiotic stress conditions in Sorghum bicolor L. PLoS One 2019; 14:e0209980. [PMID: 30650107 PMCID: PMC6335061 DOI: 10.1371/journal.pone.0209980] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2018] [Accepted: 12/14/2018] [Indexed: 12/20/2022] Open
Abstract
Late embryogenesis abundant (LEA) proteins, the space fillers or molecular shields, are the hydrophilic protective proteins which play an important role during plant development and abiotic stress. The systematic survey and characterization revealed a total of 68 LEA genes, belonging to 8 families in Sorghum bicolor. The LEA-2, a typical hydrophobic family is the most abundant family. All of them are evenly distributed on all 10 chromosomes and chromosomes 1, 2, and 3 appear to be the hot spots. Majority of the S. bicolor LEA (SbLEA) genes are intron less or have fewer introns. A total of 22 paralogous events were observed and majority of them appear to be segmental duplications. Segmental duplication played an important role in SbLEA-2 family expansion. A total of 12 orthologs were observed with Arabidopsis and 13 with Oryza sativa. Majority of them are basic in nature, and targeted by chloroplast subcellular localization. Fifteen miRNAs targeted to 25 SbLEAs appear to participate in development, as well as in abiotic stress tolerance. Promoter analysis revealed the presence of abiotic stress-responsive DRE, MYB, MYC, and GT1, biotic stress-responsive W-Box, hormone-responsive ABA, ERE, and TGA, and development-responsive SKn cis-elements. This reveals that LEA proteins play a vital role during stress tolerance and developmental processes. Using microarray data, 65 SbLEA genes were analyzed in different tissues (roots, pith, rind, internode, shoot, and leaf) which show clear tissue specific expression. qRT-PCR analysis of 23 SbLEA genes revealed their abundant expression in various tissues like roots, stems and leaves. Higher expression was noticed in stems compared to roots and leaves. Majority of the SbLEA family members were up-regulated at least in one tissue under different stress conditions. The SbLEA3-2 is the regulator, which showed abundant expression under diverse stress conditions. Present study provides new insights into the formation of LEAs in S. bicolor and to understand their role in developmental processes under stress conditions, which may be a valuable source for future research.
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Affiliation(s)
- M Nagaraju
- Department of Genetics, Osmania University, Hyderabad, India
| | - S Anil Kumar
- Department of Biotechnology, Vignan's Foundation for Science, Technology and Research, Vadlamudi, Guntur, Andhra Pradesh, India
| | - Palakolanu Sudhakar Reddy
- International Crops Research Institute for the Semi-Arid Tropics (ICRISAT), Patancheru, Hyderabad, India
| | - Anuj Kumar
- Advance Center for Computational & Applied Biotechnology, Uttarakhand Council for Biotechnology (UCB), Silk Park, Prem Nagar, Dehradun, India
| | - D Manohar Rao
- Department of Genetics, Osmania University, Hyderabad, India
| | - P B Kavi Kishor
- Department of Genetics, Osmania University, Hyderabad, India
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31
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Lin J, Ji L. Detection of MicroRNA-Mediated Target mRNA Cleavage and 3'-Uridylation in Human Cells by a SLA-RT-PCR Analysis. Methods Mol Biol 2019; 1870:125-136. [PMID: 30539551 DOI: 10.1007/978-1-4939-8808-2_9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
MicroRNA (miRNA) plays an important role in posttranscriptional regulation of gene expression by dominantly binding to the 3'-UTR regions of target mRNAs in the miRNA-induced silencing complex (miRISC), triggering off their sequential cleavage and 3'-uridylation, facilitating their degradation, repressing target gene expression, and leading to a reduced protein output. The miRNA-mediated target mRNA cleavage activity generates cleaved mRNA fragments with varied termini, which creates major technical challenges for the accurate and efficient detection and verification of cleavage sites on target mRNAs and the resulting mRNA fragments in transition. Here we described a sensitive stem-loop array reverse transcription polymerase chain reaction (SLA-RT-PCR) approach to detect and verify the miRNA-mediated target mRNA cleavage sites by determining precise sequences at the 3'- termini of cleaved mRNA fragments and their 3'-uridylation in human cells under physiological conditions. The SLA-RT-PCR methods have been demonstrated as a sensitive, cost-efficient, and high-throughput tool to systematically detect miRNA-targeted mRNA cleavage sites and fragments with 3'-uridylation in human cells.
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Affiliation(s)
- Jing Lin
- Department of Thoracic and Cardiovascular Surgery, Unit 1489, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Lin Ji
- Department of Thoracic and Cardiovascular Surgery, Unit 1489, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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32
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Yang T, Huang H, Shao Q, Yee S, Majumder T, Liu G. miR-92 Suppresses Robo1 Translation to Modulate Slit Sensitivity in Commissural Axon Guidance. Cell Rep 2018; 24:2694-2708.e6. [PMID: 30184503 DOI: 10.1016/j.celrep.2018.08.021] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Revised: 07/17/2018] [Accepted: 08/07/2018] [Indexed: 01/09/2023] Open
Abstract
Temporospatial regulation of guidance signaling is essential for axon outgrowth and pathfinding in the developing nervous system. Regulation of Robo1 levels in commissural neurons modulates Slit sensitivity facilitating proper axon guidance. The mechanisms underlying this regulation in the vertebrate nervous system are not well understood. Here, we report that miR-92, a highly conserved microRNA (miRNA), regulates chicken Robo1 expression in commissural neurons by binding to the 3' untranslated region (3' UTR) of Robo1 mRNA. miR-92 and Robo1 are differentially expressed in the developing spinal cord. miR-92 interacts with the Robo1 3'UTR to cause translational repression, but not mRNA degradation. Disruption of the miR-92/Robo1 3' UTR interaction induces premature responsiveness to Slit2 repulsion of precrossing commissural axons (CAs) in vitro and causes CA projection defects in vivo. These results indicate that miR-92 represses Robo1 expression thereby regulating Slit sensitivity to control CA projection and midline crossing.
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Affiliation(s)
- Tao Yang
- Department of Biological Sciences, University of Toledo, M.S. 601, 2801 W. Bancroft St., Toledo, OH 43606, USA
| | - Huai Huang
- Department of Biological Sciences, University of Toledo, M.S. 601, 2801 W. Bancroft St., Toledo, OH 43606, USA
| | - Qiangqiang Shao
- Department of Biological Sciences, University of Toledo, M.S. 601, 2801 W. Bancroft St., Toledo, OH 43606, USA
| | - Shirley Yee
- Department of Biological Sciences, University of Toledo, M.S. 601, 2801 W. Bancroft St., Toledo, OH 43606, USA
| | - Tanushree Majumder
- Department of Biological Sciences, University of Toledo, M.S. 601, 2801 W. Bancroft St., Toledo, OH 43606, USA
| | - Guofa Liu
- Department of Biological Sciences, University of Toledo, M.S. 601, 2801 W. Bancroft St., Toledo, OH 43606, USA.
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Yer EN, Baloglu MC, Ayan S. Identification and expression profiling of all Hsp family member genes under salinity stress in different poplar clones. Gene 2018; 678:324-336. [PMID: 30110648 DOI: 10.1016/j.gene.2018.08.049] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2018] [Revised: 07/09/2018] [Accepted: 08/10/2018] [Indexed: 12/22/2022]
Abstract
Heat shock proteins (Hsps) play a key role for regulation of the changes during different stress conditions including salinity, drought, heavy metal and extreme temperature. Molecular based studies on the response mechanisms of forest trees to abiotic stresses started in 2006 when Populus trichocarpa genome sequence was completed as a model tree species. In recent years, bioinformatic analyzes have been carried out to determine functional gene regions of tree species. In this study, sHsp, Hsp40, Hsp60, Hsp90 and Hsp100 gene family members were identified in poplar genome. Some bioinformatics analyses were conducted, such as: identification of DNA/protein sequences, chromosomal localization, gene structure, calculation of genomic duplications, determination of phylogenetic groups, examination of protected motif regions, identification of gene ontology categories, modeling of protein 3D structure, determination of miRNA targeting genes, examination of sHsp, Hsp40, Hsp60, Hsp90 and Hsp100 gene family members in transcriptome data during salinity stress. As a result of bioinformatic analyzes made on P. trichocarpa genome; 60, 145, 49, 34, 12 and 90 genes belonging to members of sHsp, Hsp40, Hsp60, Hsp70, Hsp90 and Hsp100 protein families were firstly defined within the scope of this study. A total of 390 genes belonging to all Hsps gene families were characterized using different bioinformatics tools. In addition, salinity stress was applied to Populus tremula L. (Samsun) naturally grown in Turkey, Hybrid poplar species I-214 (Populus euramericana Dode. Guinier) and Black Poplar species (Populus nigra L.), Geyve and N.03.368.A clones. The expression levels of the selected Hsps genes were determined by the qRT-PCR method. After salt stress application in various poplar clones, expression levels of genes including PtsHsp-11, PtsHsp-21, PtsHsp-36, PtHsp40-113, PtHsp40-117, PtHsp60-31, PtHsp60-33, PtHsp60-38, PtHsp60-49, PtHsp70-09, PtHsp70-12, 33, PtHsp90-09, PtHsp90-12, PtHsp100-21, and PtHsp100-75 were increased. The role of the Hsps genes during salt stress has been revealed. Together with detailed bioinformatics analyses, gene expression analysis greatly contributes to understand functions of these gene family members. This research serves as a blueprint for future studies and offers a significant clue for the further study of the functions of this important gene family. Moreover, determined genes in this study can also be used for cloning studies in agricultural practices.
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Affiliation(s)
- Esra Nurten Yer
- Silviculture Department, Faculty of Forestry, Kastamonu University, Kastamonu, Turkey
| | - Mehmet Cengiz Baloglu
- Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Kastamonu University, Turkey.
| | - Sezgin Ayan
- Silviculture Department, Faculty of Forestry, Kastamonu University, Kastamonu, Turkey
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Pohler KG, Green JA, Moley LA, Gunewardena S, Hung WT, Payton RR, Hong X, Christenson LK, Geary TW, Smith MF. Circulating microRNA as candidates for early embryonic viability in cattle. Mol Reprod Dev 2018. [PMID: 28643872 DOI: 10.1002/mrd.22856] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Blood-borne extracellular vesicles (i.e., exosomes and microvesicles) carrying microRNAs (miRNAs) could make excellent biomarkers of disease and different physiologic states, including pregnancy status. We tested the hypothesis that circulating extracellular vesicle-derived miRNAs might differentiate the pregnancy status of cows that had maintained pregnancy to Day 30 from non-pregnant cows or from those that exhibited embryonic mortality between Days 17 and 30 of gestation. Cows were randomly assigned for artificial insemination with fertile semen (n = 36) or dead semen (n = 8; control group) on Day 0 (day of estrus). Blood was collected from all animals on Day 0 and on Days 17 and 24 after artificial insemination. Cows receiving live sperm were retrospectively classified as pregnant on Day 30 (n = 17) or exhibiting embryonic mortality between Days 17 and 30 (n = 19). Extracellular vesicles from Day 17 and 24 samples were isolated from serum using ultra-centrifugation, and their presence was confirmed by nanoparticle tracking and Western blot analyses (for CD81) prior to RNA extraction. MicroRNA sequencing was performed on pregnant, embryonic-mortality, and control cows (n = 4 per day), for a total of 24 independent reactions. In total, 214 miRNAs were identified in serum, 40 of which were novel. Based on differential abundance parameters, we identified 32 differentially abundant loci, representing 27 differentially abundant mature miRNA. At Days 17 and 24, specific miRNAs (e.g., miR-25, -16b, and -3596) were identified that differentiated the pregnancy status. In summary, we identified several circulating extracellular vesicles derived miRNAs that differ in abundance between embryonic mortality and pregnant cows.
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Affiliation(s)
- Ky G Pohler
- Department of Animal Science, University of Tennessee, Knoxville, Tennessee
| | - Jonathan A Green
- Division of Animal Sciences, University of Missouri, Columbia, Missouri
| | - Laura A Moley
- Division of Animal Sciences, University of Missouri, Columbia, Missouri
| | | | - Wei-Ting Hung
- University of Kansas Medical Center, Kansas City, Kansas
| | - Rebecca R Payton
- Department of Animal Science, University of Tennessee, Knoxville, Tennessee
| | - Xiaoman Hong
- University of Kansas Medical Center, Kansas City, Kansas
| | | | - Tom W Geary
- USDA-ARS, Fort Keogh Livestock and Range Research Laboratory, Miles City, Montana
| | - Michael F Smith
- Division of Animal Sciences, University of Missouri, Columbia, Missouri
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Huang J, Lai J, Liang B, Jiang J, Ning C, Liao Y, Zang N, Wang M, Qin F, Yu J, Wei W, Ye L, Liang H. mircoRNA-3162-3p is a potential biomarker to identify new infections in HIV-1-infected patients. Gene 2018; 662:21-27. [PMID: 29627523 DOI: 10.1016/j.gene.2018.04.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2018] [Revised: 03/30/2018] [Accepted: 04/03/2018] [Indexed: 12/15/2022]
Abstract
BACKGROUND Identification of new HIV infections (HIV incidence) is critical for monitoring AIDS epidemic and assessing the effectiveness of intervention measures. However, current methods for distinguishing new infections from newly diagnosed HIV-1 patients are still imperfect. We explored utilizing miRNAs as biomarker to identify HIV new infections. METHODS According to the HIV-1 status and the estimated duration of infection (EDI), we enrolled participants and divided them into three groups: healthy control, new infection (within 1 year), and old infection (longer than 1 year). Participants were assigned into screening set or validation set. miRNA microarray was performed in screening set and the differentially expressed miRNAs were screened out. The differentially expressed miRNAs were further confirmed in validation set and HIV-1 IIIB-MT2 cells infection system. RESULTS In screening set, 5 miRNAs including miR-1291, miR-3609, miR-3162-3p, miR-874-5p and miR-4258 were screened out for their differential expression in plasma among three groups. In validation set, down- trend of miR-3162-3p was validated from healthy control, new infection to old infection groups. In HIV-1 IIIB-MT2 system, the levels of miR-3162-3p also decreased along with infection duration in vitro. Sensitivity and specificity for miR-3162-3p to distinguish new infection from old infection were 100.0% and 71.43%, respectively, with the cut-off value of 0.916. CONCLUSION miR-3162-3p in plasma could be a potential microRNA biomarker to identify HIV new infections in HIV-1 infected patients.
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Affiliation(s)
- Jiegang Huang
- Guangxi Key Laboratory of AIDS Prevention and Treatment, Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi, China
| | - Jingzhen Lai
- Guangxi Key Laboratory of AIDS Prevention and Treatment, Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi, China
| | - Bingyu Liang
- Guangxi Key Laboratory of AIDS Prevention and Treatment, Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi, China
| | - Junjun Jiang
- Guangxi Key Laboratory of AIDS Prevention and Treatment, Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi, China
| | - Chuanyi Ning
- Guangxi Collaborative Innovation Center for Biomedicine, Life Sciences Institute, Guangxi Medical University, Nanning 530021, Guangxi, China
| | - Yanyan Liao
- Guangxi Collaborative Innovation Center for Biomedicine, Life Sciences Institute, Guangxi Medical University, Nanning 530021, Guangxi, China
| | - Ning Zang
- Guangxi Collaborative Innovation Center for Biomedicine, Life Sciences Institute, Guangxi Medical University, Nanning 530021, Guangxi, China
| | - Minlian Wang
- Guangxi Key Laboratory of AIDS Prevention and Treatment, Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi, China
| | - Fengxiang Qin
- Guangxi Key Laboratory of AIDS Prevention and Treatment, Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi, China
| | - Jun Yu
- Guangxi Key Laboratory of AIDS Prevention and Treatment, Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi, China
| | - Wudi Wei
- Guangxi Key Laboratory of AIDS Prevention and Treatment, Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi, China
| | - Li Ye
- Guangxi Key Laboratory of AIDS Prevention and Treatment, Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi, China.
| | - Hao Liang
- Guangxi Key Laboratory of AIDS Prevention and Treatment, Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi, China; Guangxi Collaborative Innovation Center for Biomedicine, Life Sciences Institute, Guangxi Medical University, Nanning 530021, Guangxi, China.
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Sánchez-Ribas I, Diaz-Gimeno P, Quiñonero A, Ojeda M, Larreategui Z, Ballesteros A, Domínguez F. NGS Analysis of Human Embryo Culture Media Reveals miRNAs of Extra Embryonic Origin. Reprod Sci 2018; 26:214-222. [PMID: 29587610 DOI: 10.1177/1933719118766252] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Our objective in this work was to isolate, identify, and compare micro-RNAs (miRNAs) found in spent culture media of euploid and aneuploid in vitro fertilization (IVF) embryos. Seventy-two embryos from 62 patients were collected, and their spent media were retained. A total of 108 spent conditioned media samples were analyzed (n = 36 day 3 euploid embryos, n = 36 day 3 aneuploid embryos, and n = 36 matched control media). Fifty hed-control media embryos were analyzed using next-generation sequencing (NGS) technology. We detected 53 known human miRNAs present in the spent conditioned media of euploid and aneuploid IVF embryos. miR-181b-5p and miR-191-5p were found the most represented. We validated our results by quantitative polymerase chain reaction (qPCR), but no significant results were obtained between the groups. In conclusion, we obtained the list of miRNAs present in the spent conditioned media from euploid and aneuploid IVF embryos, but our data suggest that these miRNAs could have a nonembryonic origin.
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Affiliation(s)
- Immaculada Sánchez-Ribas
- 1 IVI Barcelona, Barcelona, Spain.,2 Fundación IVI-Instituto Universitario IVI, INCLIVA, Valencia, Spain
| | | | - Alicia Quiñonero
- 2 Fundación IVI-Instituto Universitario IVI, INCLIVA, Valencia, Spain
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Shang G, Wang Y, Xu Y, Zhang S, Sun X, Guan H, Zhao X, Wang Y, Li Y, Zhao G. Long non-coding RNA TCONS_00041960 enhances osteogenesis and inhibits adipogenesis of rat bone marrow mesenchymal stem cell by targeting miR-204-5p and miR-125a-3p. J Cell Physiol 2018; 233:6041-6051. [PMID: 29319166 PMCID: PMC5947671 DOI: 10.1002/jcp.26424] [Citation(s) in RCA: 65] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2017] [Accepted: 01/05/2018] [Indexed: 12/15/2022]
Abstract
A growing number of long non‐coding RNAs (lncRNAs) have been found to be involved in diverse biological processes such as cell cycle regulation, embryonic development, and cell differentiation. However, limited knowledge is available concerning the underlying mechanisms of lncRNA functions. In this study, we found down‐regulation of TCONS_00041960 during adipogenic and osteogenic differentiation of glucocorticoid‐treated bone marrow mesenchymal stem cells (BMSCs). Furthermore, up‐regulation of TCONS_00041960 promoted expression of osteogenic genes Runx2, osterix, and osteocalcin, and anti‐adipogenic gene glucocorticoid‐induced leucine zipper (GILZ). Conversely, expression of adipocyte‐specific markers was decreased in the presence of over‐expressed TCONS_00041960. Mechanistically, we determined that TCONS_00041960 as a competing endogenous RNA interacted with miR‐204‐5p and miR‐125a‐3p to regulate Runx2 and GILZ, respectively. Overall, we identified a new TCONS_00041960‐miR‐204‐5p/miR‐125a‐3p‐Runx2/GILZ axis involved in regulation of adipogenic and osteogenic differentiation of glucocorticoid‐treated BMSCs.
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Affiliation(s)
- Guowei Shang
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yadong Wang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
| | - Yan Xu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
| | - Shanfeng Zhang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
| | - Xiaoya Sun
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
| | - Hongya Guan
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
| | - Xuefeng Zhao
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
| | - Yisheng Wang
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yuebai Li
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
| | - Guoqiang Zhao
- Department of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
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PEAK1, acting as a tumor promoter in colorectal cancer, is regulated by the EGFR/KRas signaling axis and miR-181d. Cell Death Dis 2018; 9:271. [PMID: 29449544 PMCID: PMC5833579 DOI: 10.1038/s41419-018-0320-8] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2017] [Revised: 01/12/2018] [Accepted: 01/15/2018] [Indexed: 12/12/2022]
Abstract
PEAK1 is upregulated in multiple human malignancies and has been associated with tumor invasion and metastasis, but little is known about the role of PEAK1 in colorectal cancer (CRC) progression. We investigated the expression pattern, function and regulatory mechanisms of PEAK1 in CRC. Here, we found that PEAK1 is overexpressed in CRC tissues and that high PEAK1 expression predicts poor survival in colon cancer but not rectal cancer. Functionally, silencing PEAK1 inhibits cell proliferation, migration, and invasion in vitro and inhibits the growth of tumor xenografts in nude mice. Mechanistic studies revealed that PEAK1 is induced by epidermal growth factor receptor (EGFR) signaling and that PEAK1 is required for KRas-induced CRC cell growth and metastasis. Furthermore, we demonstrated that miR-181d directly targets PEAK1. Ectopic expression of miR-181d reduces the expression of PEAK1 and inhibits the growth and metastasis of CRC cells in vitro. Clinically, miR-181d is downregulated in CRC samples, and low miR-181d is correlated with poor patient survival. Our study demonstrates the importance of PEAK1 in CRC progression and suggests a potential mechanism by which increasing PEAK1 expression in CRC might be the result of EGFR/KRas signal activation and consequent miR-181d repression.
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Balzano F, Cruciani S, Basoli V, Santaniello S, Facchin F, Ventura C, Maioli M. MiR200 and miR302: Two Big Families Influencing Stem Cell Behavior. Molecules 2018; 23:282. [PMID: 29385685 PMCID: PMC6017081 DOI: 10.3390/molecules23020282] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2018] [Revised: 01/25/2018] [Accepted: 01/27/2018] [Indexed: 02/08/2023] Open
Abstract
In this review, we described different factors that modulate pluripotency in stem cells, in particular we aimed at following the steps of two large families of miRNAs: the miR-200 family and the miR-302 family. We analyzed some factors tuning stem cells behavior as TGF-β, which plays a pivotal role in pluripotency inhibition together with specific miRNAs, reactive oxygen species (ROS), but also hypoxia, and physical stimuli, such as ad hoc conveyed electromagnetic fields. TGF-β plays a crucial role in the suppression of pluripotency thus influencing the achievement of a specific phenotype. ROS concentration can modulate TGF-β activation that in turns down regulates miR-200 and miR-302. These two miRNAs are usually requested to maintain pluripotency, while they are down-regulated during the acquirement of a specific cellular phenotype. Moreover, also physical stimuli, such as extremely-low frequency electromagnetic fields or high-frequency electromagnetic fields conveyed with a radioelectric asymmetric conveyer (REAC), and hypoxia can deeply influence stem cell behavior by inducing the appearance of specific phenotypes, as well as a direct reprogramming of somatic cells. Unraveling the molecular mechanisms underlying the complex interplay between externally applied stimuli and epigenetic events could disclose novel target molecules to commit stem cell fate.
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Affiliation(s)
- Francesca Balzano
- Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy.
| | - Sara Cruciani
- Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy.
- Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, Innovation Accelerator, CNR, Via Piero Gobetti 101, 40129 Bologna, Italy.
| | - Valentina Basoli
- Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy.
- Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, Innovation Accelerator, CNR, Via Piero Gobetti 101, 40129 Bologna, Italy.
| | - Sara Santaniello
- Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy.
- Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, Innovation Accelerator, CNR, Via Piero Gobetti 101, 40129 Bologna, Italy.
| | - Federica Facchin
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Via Massarenti 9, 40138 Bologna, Italy.
| | - Carlo Ventura
- Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, Innovation Accelerator, CNR, Via Piero Gobetti 101, 40129 Bologna, Italy.
- GUNA ATTRE (Advanced Therapies and Tissue REgeneration), Innovation Accelerator, CNR, Via Piero Gobetti 101, 40129 Bologna, Italy.
| | - Margherita Maioli
- Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy.
- Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, Innovation Accelerator, CNR, Via Piero Gobetti 101, 40129 Bologna, Italy.
- Istituto di RicercaGenetica e Biomedica, Consiglio Nazionaledelle Ricerche (CNR), Monserrato, 09042 Cagliari, Italy.
- Center for Developmental Biology and Reprogramming (CEDEBIOR), Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy.
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Magwanga RO, Lu P, Kirungu JN, Lu H, Wang X, Cai X, Zhou Z, Zhang Z, Salih H, Wang K, Liu F. Characterization of the late embryogenesis abundant (LEA) proteins family and their role in drought stress tolerance in upland cotton. BMC Genet 2018; 19:6. [PMID: 29334890 PMCID: PMC5769447 DOI: 10.1186/s12863-017-0596-1] [Citation(s) in RCA: 133] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Accepted: 12/29/2017] [Indexed: 12/20/2022] Open
Abstract
Background Late embryogenesis abundant (LEA) proteins are large groups of hydrophilic proteins with major role in drought and other abiotic stresses tolerance in plants. In-depth study and characterization of LEA protein families have been carried out in other plants, but not in upland cotton. The main aim of this research work was to characterize the late embryogenesis abundant (LEA) protein families and to carry out gene expression analysis to determine their potential role in drought stress tolerance in upland cotton. Increased cotton production in the face of declining precipitation and availability of fresh water for agriculture use is the focus for breeders, cotton being the backbone of textile industries and a cash crop for many countries globally. Results In this work, a total of 242, 136 and 142 LEA genes were identified in G. hirsutum, G. arboreum and G. raimondii respectively. The identified genes were classified into eight groups based on their conserved domain and phylogenetic tree analysis. LEA 2 were the most abundant, this could be attributed to their hydrophobic character. Upland cotton LEA genes have fewer introns and are distributed in all chromosomes. Majority of the duplicated LEA genes were segmental. Syntenic analysis showed that greater percentages of LEA genes are conserved. Segmental gene duplication played a key role in the expansion of LEA genes. Sixty three miRNAs were found to target 89 genes, such as miR164, ghr-miR394 among others. Gene ontology analysis revealed that LEA genes are involved in desiccation and defense responses. Almost all the LEA genes in their promoters contained ABRE, MBS, W-Box and TAC-elements, functionally known to be involved in drought stress and other stress responses. Majority of the LEA genes were involved in secretory pathways. Expression profile analysis indicated that most of the LEA genes were highly expressed in drought tolerant cultivars Gossypium tomentosum as opposed to drought susceptible, G. hirsutum. The tolerant genotypes have a greater ability to modulate genes under drought stress than the more susceptible upland cotton cultivars. Conclusion The finding provides comprehensive information on LEA genes in upland cotton, G. hirsutum and possible function in plants under drought stress. Electronic supplementary material The online version of this article (10.1186/s12863-017-0596-1) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Richard Odongo Magwanga
- Institute of Cotton Research, Chinese Academy of Agricultural Science (ICR, CAAS)/State Key Laboratory of Cotton Biology, Anyang, 455000, China.,School of physical and biological sciences (SPBS), Main campus, Jaramogi Oginga Odinga University of Science and Technology (JOOUST), P.O Box 210-40601, Bondo, Kenya
| | - Pu Lu
- Institute of Cotton Research, Chinese Academy of Agricultural Science (ICR, CAAS)/State Key Laboratory of Cotton Biology, Anyang, 455000, China
| | - Joy Nyangasi Kirungu
- Institute of Cotton Research, Chinese Academy of Agricultural Science (ICR, CAAS)/State Key Laboratory of Cotton Biology, Anyang, 455000, China
| | - Hejun Lu
- Institute of Cotton Research, Chinese Academy of Agricultural Science (ICR, CAAS)/State Key Laboratory of Cotton Biology, Anyang, 455000, China
| | - Xingxing Wang
- Institute of Cotton Research, Chinese Academy of Agricultural Science (ICR, CAAS)/State Key Laboratory of Cotton Biology, Anyang, 455000, China
| | - Xiaoyan Cai
- Institute of Cotton Research, Chinese Academy of Agricultural Science (ICR, CAAS)/State Key Laboratory of Cotton Biology, Anyang, 455000, China
| | - Zhongli Zhou
- Institute of Cotton Research, Chinese Academy of Agricultural Science (ICR, CAAS)/State Key Laboratory of Cotton Biology, Anyang, 455000, China
| | - Zhenmei Zhang
- Institute of Cotton Research, Chinese Academy of Agricultural Science (ICR, CAAS)/State Key Laboratory of Cotton Biology, Anyang, 455000, China
| | - Haron Salih
- Institute of Cotton Research, Chinese Academy of Agricultural Science (ICR, CAAS)/State Key Laboratory of Cotton Biology, Anyang, 455000, China
| | - Kunbo Wang
- Institute of Cotton Research, Chinese Academy of Agricultural Science (ICR, CAAS)/State Key Laboratory of Cotton Biology, Anyang, 455000, China.
| | - Fang Liu
- Institute of Cotton Research, Chinese Academy of Agricultural Science (ICR, CAAS)/State Key Laboratory of Cotton Biology, Anyang, 455000, China.
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Magwanga RO, Lu P, Kirungu JN, Lu H, Wang X, Cai X, Zhou Z, Zhang Z, Salih H, Wang K, Liu F. Characterization of the late embryogenesis abundant (LEA) proteins family and their role in drought stress tolerance in upland cotton. BMC Genet 2018; 19:6. [PMID: 29334890 PMCID: PMC5769447 DOI: 10.1007/s11033-012-2250-3fang 10.1186/s12863-017-0596-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Accepted: 12/29/2017] [Indexed: 05/22/2023] Open
Abstract
BACKGROUND Late embryogenesis abundant (LEA) proteins are large groups of hydrophilic proteins with major role in drought and other abiotic stresses tolerance in plants. In-depth study and characterization of LEA protein families have been carried out in other plants, but not in upland cotton. The main aim of this research work was to characterize the late embryogenesis abundant (LEA) protein families and to carry out gene expression analysis to determine their potential role in drought stress tolerance in upland cotton. Increased cotton production in the face of declining precipitation and availability of fresh water for agriculture use is the focus for breeders, cotton being the backbone of textile industries and a cash crop for many countries globally. RESULTS In this work, a total of 242, 136 and 142 LEA genes were identified in G. hirsutum, G. arboreum and G. raimondii respectively. The identified genes were classified into eight groups based on their conserved domain and phylogenetic tree analysis. LEA 2 were the most abundant, this could be attributed to their hydrophobic character. Upland cotton LEA genes have fewer introns and are distributed in all chromosomes. Majority of the duplicated LEA genes were segmental. Syntenic analysis showed that greater percentages of LEA genes are conserved. Segmental gene duplication played a key role in the expansion of LEA genes. Sixty three miRNAs were found to target 89 genes, such as miR164, ghr-miR394 among others. Gene ontology analysis revealed that LEA genes are involved in desiccation and defense responses. Almost all the LEA genes in their promoters contained ABRE, MBS, W-Box and TAC-elements, functionally known to be involved in drought stress and other stress responses. Majority of the LEA genes were involved in secretory pathways. Expression profile analysis indicated that most of the LEA genes were highly expressed in drought tolerant cultivars Gossypium tomentosum as opposed to drought susceptible, G. hirsutum. The tolerant genotypes have a greater ability to modulate genes under drought stress than the more susceptible upland cotton cultivars. CONCLUSION The finding provides comprehensive information on LEA genes in upland cotton, G. hirsutum and possible function in plants under drought stress.
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Affiliation(s)
- Richard Odongo Magwanga
- Institute of Cotton Research, Chinese Academy of Agricultural Science (ICR, CAAS)/State Key Laboratory of Cotton Biology, Anyang, 455000 China
- School of physical and biological sciences (SPBS), Main campus, Jaramogi Oginga Odinga University of Science and Technology (JOOUST), P.O Box 210-40601, Bondo, Kenya
| | - Pu Lu
- Institute of Cotton Research, Chinese Academy of Agricultural Science (ICR, CAAS)/State Key Laboratory of Cotton Biology, Anyang, 455000 China
| | - Joy Nyangasi Kirungu
- Institute of Cotton Research, Chinese Academy of Agricultural Science (ICR, CAAS)/State Key Laboratory of Cotton Biology, Anyang, 455000 China
| | - Hejun Lu
- Institute of Cotton Research, Chinese Academy of Agricultural Science (ICR, CAAS)/State Key Laboratory of Cotton Biology, Anyang, 455000 China
| | - Xingxing Wang
- Institute of Cotton Research, Chinese Academy of Agricultural Science (ICR, CAAS)/State Key Laboratory of Cotton Biology, Anyang, 455000 China
| | - Xiaoyan Cai
- Institute of Cotton Research, Chinese Academy of Agricultural Science (ICR, CAAS)/State Key Laboratory of Cotton Biology, Anyang, 455000 China
| | - Zhongli Zhou
- Institute of Cotton Research, Chinese Academy of Agricultural Science (ICR, CAAS)/State Key Laboratory of Cotton Biology, Anyang, 455000 China
| | - Zhenmei Zhang
- Institute of Cotton Research, Chinese Academy of Agricultural Science (ICR, CAAS)/State Key Laboratory of Cotton Biology, Anyang, 455000 China
| | - Haron Salih
- Institute of Cotton Research, Chinese Academy of Agricultural Science (ICR, CAAS)/State Key Laboratory of Cotton Biology, Anyang, 455000 China
| | - Kunbo Wang
- Institute of Cotton Research, Chinese Academy of Agricultural Science (ICR, CAAS)/State Key Laboratory of Cotton Biology, Anyang, 455000 China
| | - Fang Liu
- Institute of Cotton Research, Chinese Academy of Agricultural Science (ICR, CAAS)/State Key Laboratory of Cotton Biology, Anyang, 455000 China
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Niu D, Zhang X, Song X, Wang Z, Li Y, Qiao L, Wang Z, Liu J, Deng Y, He Z, Yang D, Liu R, Wang Y, Zhao H. Deep Sequencing Uncovers Rice Long siRNAs and Its Involvement in Immunity Against Rhizoctonia solani. PHYTOPATHOLOGY 2018; 108:60-69. [PMID: 28876208 DOI: 10.1094/phyto-03-17-0119-r] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
Small RNA (sRNA) is a class of noncoding RNA that can silence the expression of target genes. In rice, the majority of characterized sRNAs are within the range of 21 to 24 nucleotides (nt) long, whose biogenesis and function are associated with a specific sets of components, such as Dicer-like (OsDCLs) and Argonaute proteins (OsAGOs). Rice sRNAs longer than 24 nt are occasionally reported, with biogenesis and functional mechanism uninvestigated, especially in a context of defense responses against pathogen infection. By using deep sequencing, we identified a group of rice long small interfering RNAs (lsiRNAs) that are within the range of 25 to 40 nt in length. Our results show that some rice lsiRNAs are differentially expressed upon infection of Rhizoctonia solani, the causal agent of the rice sheath blight disease. Bioinformatic analysis and experimental validation indicate that some rice lsiRNAs can target defense-related genes. We further demonstrate that rice lsiRNAs are neither derived from RNA degradation nor originated as secondary small interfering RNAs (siRNAs). Moreover, lsiRNAs require OsDCL4 for biogenesis and OsAGO18 for function. Therefore, our study indicates that rice lsiRNAs are a unique class of endogenous sRNAs produced in rice, which may participate in response against pathogens.
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Affiliation(s)
- Dongdong Niu
- First, second, third, fourth, sixth, seventh, and fourteenth authors: College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China; first, second, third, fourth, sixth, and fourteenth authors: Key Laboratory of Integrated Management of Crop Diseases and Pests (Nanjing Agricultural University), Ministry of Education; second author: Institute of Industrial Crops, Shanxi Academy of Agricultural Sciences, Taiyuan 030000, Shanxi, China; fifth and twelfth authors: Shanghai Center for Plant Stress Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, China; eighth, ninth, and tenth authors: National Key Laboratory of Plant Molecular Genetics, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China; eleventh author: College of Agriculture, Nanjing Agricultural University, Nanjing 210095, China; and thirteenth author: State Key Laboratory Breeding Base for Zhejiang Sustainable Pest and Disease Control, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China
| | - Xin Zhang
- First, second, third, fourth, sixth, seventh, and fourteenth authors: College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China; first, second, third, fourth, sixth, and fourteenth authors: Key Laboratory of Integrated Management of Crop Diseases and Pests (Nanjing Agricultural University), Ministry of Education; second author: Institute of Industrial Crops, Shanxi Academy of Agricultural Sciences, Taiyuan 030000, Shanxi, China; fifth and twelfth authors: Shanghai Center for Plant Stress Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, China; eighth, ninth, and tenth authors: National Key Laboratory of Plant Molecular Genetics, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China; eleventh author: College of Agriculture, Nanjing Agricultural University, Nanjing 210095, China; and thirteenth author: State Key Laboratory Breeding Base for Zhejiang Sustainable Pest and Disease Control, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China
| | - Xiaoou Song
- First, second, third, fourth, sixth, seventh, and fourteenth authors: College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China; first, second, third, fourth, sixth, and fourteenth authors: Key Laboratory of Integrated Management of Crop Diseases and Pests (Nanjing Agricultural University), Ministry of Education; second author: Institute of Industrial Crops, Shanxi Academy of Agricultural Sciences, Taiyuan 030000, Shanxi, China; fifth and twelfth authors: Shanghai Center for Plant Stress Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, China; eighth, ninth, and tenth authors: National Key Laboratory of Plant Molecular Genetics, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China; eleventh author: College of Agriculture, Nanjing Agricultural University, Nanjing 210095, China; and thirteenth author: State Key Laboratory Breeding Base for Zhejiang Sustainable Pest and Disease Control, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China
| | - Zhihui Wang
- First, second, third, fourth, sixth, seventh, and fourteenth authors: College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China; first, second, third, fourth, sixth, and fourteenth authors: Key Laboratory of Integrated Management of Crop Diseases and Pests (Nanjing Agricultural University), Ministry of Education; second author: Institute of Industrial Crops, Shanxi Academy of Agricultural Sciences, Taiyuan 030000, Shanxi, China; fifth and twelfth authors: Shanghai Center for Plant Stress Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, China; eighth, ninth, and tenth authors: National Key Laboratory of Plant Molecular Genetics, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China; eleventh author: College of Agriculture, Nanjing Agricultural University, Nanjing 210095, China; and thirteenth author: State Key Laboratory Breeding Base for Zhejiang Sustainable Pest and Disease Control, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China
| | - Yanqiang Li
- First, second, third, fourth, sixth, seventh, and fourteenth authors: College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China; first, second, third, fourth, sixth, and fourteenth authors: Key Laboratory of Integrated Management of Crop Diseases and Pests (Nanjing Agricultural University), Ministry of Education; second author: Institute of Industrial Crops, Shanxi Academy of Agricultural Sciences, Taiyuan 030000, Shanxi, China; fifth and twelfth authors: Shanghai Center for Plant Stress Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, China; eighth, ninth, and tenth authors: National Key Laboratory of Plant Molecular Genetics, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China; eleventh author: College of Agriculture, Nanjing Agricultural University, Nanjing 210095, China; and thirteenth author: State Key Laboratory Breeding Base for Zhejiang Sustainable Pest and Disease Control, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China
| | - Lulu Qiao
- First, second, third, fourth, sixth, seventh, and fourteenth authors: College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China; first, second, third, fourth, sixth, and fourteenth authors: Key Laboratory of Integrated Management of Crop Diseases and Pests (Nanjing Agricultural University), Ministry of Education; second author: Institute of Industrial Crops, Shanxi Academy of Agricultural Sciences, Taiyuan 030000, Shanxi, China; fifth and twelfth authors: Shanghai Center for Plant Stress Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, China; eighth, ninth, and tenth authors: National Key Laboratory of Plant Molecular Genetics, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China; eleventh author: College of Agriculture, Nanjing Agricultural University, Nanjing 210095, China; and thirteenth author: State Key Laboratory Breeding Base for Zhejiang Sustainable Pest and Disease Control, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China
| | - Zhaoyun Wang
- First, second, third, fourth, sixth, seventh, and fourteenth authors: College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China; first, second, third, fourth, sixth, and fourteenth authors: Key Laboratory of Integrated Management of Crop Diseases and Pests (Nanjing Agricultural University), Ministry of Education; second author: Institute of Industrial Crops, Shanxi Academy of Agricultural Sciences, Taiyuan 030000, Shanxi, China; fifth and twelfth authors: Shanghai Center for Plant Stress Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, China; eighth, ninth, and tenth authors: National Key Laboratory of Plant Molecular Genetics, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China; eleventh author: College of Agriculture, Nanjing Agricultural University, Nanjing 210095, China; and thirteenth author: State Key Laboratory Breeding Base for Zhejiang Sustainable Pest and Disease Control, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China
| | - Junzhong Liu
- First, second, third, fourth, sixth, seventh, and fourteenth authors: College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China; first, second, third, fourth, sixth, and fourteenth authors: Key Laboratory of Integrated Management of Crop Diseases and Pests (Nanjing Agricultural University), Ministry of Education; second author: Institute of Industrial Crops, Shanxi Academy of Agricultural Sciences, Taiyuan 030000, Shanxi, China; fifth and twelfth authors: Shanghai Center for Plant Stress Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, China; eighth, ninth, and tenth authors: National Key Laboratory of Plant Molecular Genetics, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China; eleventh author: College of Agriculture, Nanjing Agricultural University, Nanjing 210095, China; and thirteenth author: State Key Laboratory Breeding Base for Zhejiang Sustainable Pest and Disease Control, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China
| | - Yiwen Deng
- First, second, third, fourth, sixth, seventh, and fourteenth authors: College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China; first, second, third, fourth, sixth, and fourteenth authors: Key Laboratory of Integrated Management of Crop Diseases and Pests (Nanjing Agricultural University), Ministry of Education; second author: Institute of Industrial Crops, Shanxi Academy of Agricultural Sciences, Taiyuan 030000, Shanxi, China; fifth and twelfth authors: Shanghai Center for Plant Stress Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, China; eighth, ninth, and tenth authors: National Key Laboratory of Plant Molecular Genetics, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China; eleventh author: College of Agriculture, Nanjing Agricultural University, Nanjing 210095, China; and thirteenth author: State Key Laboratory Breeding Base for Zhejiang Sustainable Pest and Disease Control, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China
| | - Zuhua He
- First, second, third, fourth, sixth, seventh, and fourteenth authors: College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China; first, second, third, fourth, sixth, and fourteenth authors: Key Laboratory of Integrated Management of Crop Diseases and Pests (Nanjing Agricultural University), Ministry of Education; second author: Institute of Industrial Crops, Shanxi Academy of Agricultural Sciences, Taiyuan 030000, Shanxi, China; fifth and twelfth authors: Shanghai Center for Plant Stress Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, China; eighth, ninth, and tenth authors: National Key Laboratory of Plant Molecular Genetics, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China; eleventh author: College of Agriculture, Nanjing Agricultural University, Nanjing 210095, China; and thirteenth author: State Key Laboratory Breeding Base for Zhejiang Sustainable Pest and Disease Control, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China
| | - Donglei Yang
- First, second, third, fourth, sixth, seventh, and fourteenth authors: College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China; first, second, third, fourth, sixth, and fourteenth authors: Key Laboratory of Integrated Management of Crop Diseases and Pests (Nanjing Agricultural University), Ministry of Education; second author: Institute of Industrial Crops, Shanxi Academy of Agricultural Sciences, Taiyuan 030000, Shanxi, China; fifth and twelfth authors: Shanghai Center for Plant Stress Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, China; eighth, ninth, and tenth authors: National Key Laboratory of Plant Molecular Genetics, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China; eleventh author: College of Agriculture, Nanjing Agricultural University, Nanjing 210095, China; and thirteenth author: State Key Laboratory Breeding Base for Zhejiang Sustainable Pest and Disease Control, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China
| | - Renyi Liu
- First, second, third, fourth, sixth, seventh, and fourteenth authors: College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China; first, second, third, fourth, sixth, and fourteenth authors: Key Laboratory of Integrated Management of Crop Diseases and Pests (Nanjing Agricultural University), Ministry of Education; second author: Institute of Industrial Crops, Shanxi Academy of Agricultural Sciences, Taiyuan 030000, Shanxi, China; fifth and twelfth authors: Shanghai Center for Plant Stress Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, China; eighth, ninth, and tenth authors: National Key Laboratory of Plant Molecular Genetics, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China; eleventh author: College of Agriculture, Nanjing Agricultural University, Nanjing 210095, China; and thirteenth author: State Key Laboratory Breeding Base for Zhejiang Sustainable Pest and Disease Control, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China
| | - Yanli Wang
- First, second, third, fourth, sixth, seventh, and fourteenth authors: College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China; first, second, third, fourth, sixth, and fourteenth authors: Key Laboratory of Integrated Management of Crop Diseases and Pests (Nanjing Agricultural University), Ministry of Education; second author: Institute of Industrial Crops, Shanxi Academy of Agricultural Sciences, Taiyuan 030000, Shanxi, China; fifth and twelfth authors: Shanghai Center for Plant Stress Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, China; eighth, ninth, and tenth authors: National Key Laboratory of Plant Molecular Genetics, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China; eleventh author: College of Agriculture, Nanjing Agricultural University, Nanjing 210095, China; and thirteenth author: State Key Laboratory Breeding Base for Zhejiang Sustainable Pest and Disease Control, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China
| | - Hongwei Zhao
- First, second, third, fourth, sixth, seventh, and fourteenth authors: College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China; first, second, third, fourth, sixth, and fourteenth authors: Key Laboratory of Integrated Management of Crop Diseases and Pests (Nanjing Agricultural University), Ministry of Education; second author: Institute of Industrial Crops, Shanxi Academy of Agricultural Sciences, Taiyuan 030000, Shanxi, China; fifth and twelfth authors: Shanghai Center for Plant Stress Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, China; eighth, ninth, and tenth authors: National Key Laboratory of Plant Molecular Genetics, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China; eleventh author: College of Agriculture, Nanjing Agricultural University, Nanjing 210095, China; and thirteenth author: State Key Laboratory Breeding Base for Zhejiang Sustainable Pest and Disease Control, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China
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Sun G, Lu Y, Li Y, Mao J, Zhang J, Jin Y, Li Y, Sun Y, Liu L, Li L. miR-19a protects cardiomyocytes from hypoxia/reoxygenation-induced apoptosis via PTEN/PI3K/p-Akt pathway. Biosci Rep 2017; 37:BSR20170899. [PMID: 29054970 PMCID: PMC5715126 DOI: 10.1042/bsr20170899] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2017] [Revised: 11/10/2017] [Accepted: 10/18/2017] [Indexed: 12/24/2022] Open
Abstract
miRNAs have been implicated in processing of cardiac hypoxia/reoxygenation (H/R)-induced injury. Recent studies demonstrated that miR-19a might provide a potential cardioprotective effect on myocardial disease. However, the effect of miR-19a in regulating myocardial ischemic injury has not been previously addressed. The present study was to investigate the effect of miR-19a on myocardial ischemic injury and identified the potential molecular mechanisms involved. Using the H/R model of rat cardiomyocytes H9C2 in vitro, we found that miR-19a was in low expression in H9C2 cells after H/R treatment and H/R dramatically decreased cardiomyocyte viability, and increased lactate dehydrogenase (LDH) release and cardiomyocyte apoptosis, which were attenuated by co-transfection with miR-19a mimic. Dual-luciferase reporter assay and Western blotting assay revealed that PTEN was a direct target gene of miR-19a, and miR-19a suppressed the expression of PTEN via binding to its 3'-UTR. We further identified that overexpression of miR-19a inhibited the expression of PTEN at the mRNA and protein levels. Moreover, PTEN was highly expressed in H/R H9C2 cells and the apoptosis induced by H/R was associated with the increase in PTEN expression. Importantly, miR-19a mimic significantly increased p-Akt levels under H/R. In conclusion, our findings indicate that miR-19a could protect against H/R-induced cardiomyocyte apoptosis by inhibiting PTEN /PI3K/p-Akt signaling pathway.
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Affiliation(s)
- Guochao Sun
- Deparment of Pathology and Forensics, Dalian Medical University, No.9 West Section, Lvshun Road, Dalian 116044, China
| | - Ying Lu
- Teaching Laboratory of Morphology, Dalian Medical University, No.9 West Section, Lvshun Road, Dalian 116044, China
| | - Yingxia Li
- Department of Spine Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Jun Mao
- Deparment of Pathology and Forensics, Dalian Medical University, No.9 West Section, Lvshun Road, Dalian 116044, China
| | - Jun Zhang
- Teaching Affairs Department, Dalian Medical University, No.9 West Section, Lvshun Road, Dalian 116044, China
| | - Yanling Jin
- Department of Pathology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Yan Li
- Department of Anatomy, Dalian Medical University, No.9 West Section, Lvshun Road, Dalian 116044, China
| | - Yan Sun
- Deparment of Pathology and Forensics, Dalian Medical University, No.9 West Section, Lvshun Road, Dalian 116044, China
| | - Lei Liu
- Deparment of Pathology and Forensics, Dalian Medical University, No.9 West Section, Lvshun Road, Dalian 116044, China
| | - Lianhong Li
- Deparment of Pathology and Forensics, Dalian Medical University, No.9 West Section, Lvshun Road, Dalian 116044, China
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Kang L, Yang C, Wu H, Chen Q, Huang L, Li X, Tang H, Jiang Y. miR-26a-5p Regulates TNRC6A Expression and Facilitates Theca Cell Proliferation in Chicken Ovarian Follicles. DNA Cell Biol 2017; 36:922-929. [PMID: 28876086 DOI: 10.1089/dna.2017.3863] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Ovarian theca cells play an indispensable role in ovarian follicular development and hormone secretion. miR-26a-5p was reported to be differentially expressed in mature and immature chicken ovaries in our previous study; however, the role of miR-26a-5p in regulating ovarian follicle function is still unclear. In this study, we demonstrated that the expression dynamics of TNRC6A mRNA in either chicken ovaries or follicles showed an opposite trend compared with that of chicken miR-26a-5p expression. miR-26a-5p inhibited TNRC6A mRNA expression by directly targeting its 3'-untranslated region in cultured chicken theca cells. Overexpression of miR-26a-5p promoted chicken follicular theca cell proliferation in vitro. Furthermore, overexpression of miR-26a-5p and knockdown of TNRC6A significantly upregulated the antiapoptotic BCL-2 gene. Taken together, this study revealed the expression dynamics of miR-26a-5p and TNRC6A in chicken ovaries and ovarian follicles and the relationship between the expression of miR-26a-5p and TNRC6A in chicken ovarian theca cells. These results suggest that miR-26a-5p facilitates chicken ovarian theca cell proliferation by targeting the TNRC6A gene.
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Affiliation(s)
- Li Kang
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Veterinary Medicine, Shandong Agricultural University , Taian, People's Republic of China
| | - Chunhong Yang
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Veterinary Medicine, Shandong Agricultural University , Taian, People's Republic of China
| | - Haizhen Wu
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Veterinary Medicine, Shandong Agricultural University , Taian, People's Republic of China
| | - Qiuyue Chen
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Veterinary Medicine, Shandong Agricultural University , Taian, People's Republic of China
| | - Libo Huang
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Veterinary Medicine, Shandong Agricultural University , Taian, People's Republic of China
| | - Xianyao Li
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Veterinary Medicine, Shandong Agricultural University , Taian, People's Republic of China
| | - Hui Tang
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Veterinary Medicine, Shandong Agricultural University , Taian, People's Republic of China
| | - Yunliang Jiang
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Veterinary Medicine, Shandong Agricultural University , Taian, People's Republic of China
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Overexpression of Chromosome 21 miRNAs May Affect Mitochondrial Function in the Hearts of Down Syndrome Fetuses. Int J Genomics 2017; 2017:8737649. [PMID: 29057256 PMCID: PMC5605795 DOI: 10.1155/2017/8737649] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2017] [Revised: 07/20/2017] [Accepted: 08/02/2017] [Indexed: 12/03/2022] Open
Abstract
Dosage-dependent upregulation of most of chromosome 21 (Hsa21) genes has been demonstrated in heart tissues of fetuses with Down syndrome (DS). Also miRNAs might play important roles in the cardiac phenotype as they are highly expressed in the heart and regulate cardiac development. Five Hsa21 miRNAs have been well studied in the past: miR-99a-5p, miR-125b-2-5p, let-7c-5p, miR-155-5p, and miR-802-5p but few information is available about their expression in trisomic tissues. In this study, we evaluated the expression of these miRNAs in heart tissues from DS fetuses, showing that miR-99a-5p, miR-155-5p, and let-7c-5p were overexpressed in trisomic hearts. To investigate their role, predicted targets were obtained from different databases and cross-validated using the gene expression profiling dataset we previously generated for fetal hearts. Eighty-five targets of let-7c-5p, 33 of miR-155-5p, and 10 of miR-99a-5p were expressed in fetal heart and downregulated in trisomic hearts. As nuclear encoded mitochondrial genes were found downregulated in trisomic hearts and mitochondrial dysfunction is a hallmark of DS phenotypes, we put special attention to let-7c-5p and miR-155-5p targets downregulated in DS fetal hearts and involved in mitochondrial function. The let-7c-5p predicted target SLC25A4/ANT1 was identified as a possible candidate for both mitochondrial and cardiac anomalies.
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Höti N, Yang S, Aiyetan P, Kumar B, Hu Y, Clark D, Eroglu AU, Shah P, Johnson T, Chowdery WH, Zhang H, Rodriguez R. Overexpression of Exportin-5 Overrides the Inhibitory Effect of miRNAs Regulation Control and Stabilize Proteins via Posttranslation Modifications in Prostate Cancer. Neoplasia 2017; 19:817-829. [PMID: 28881308 PMCID: PMC5587889 DOI: 10.1016/j.neo.2017.07.008] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2017] [Revised: 07/28/2017] [Accepted: 07/31/2017] [Indexed: 01/21/2023] Open
Abstract
Although XPO5 has been characterized to have tumor-suppressor features in the miRNA biogenesis pathway, the impact of altered expression of XPO5 in cancers is unexplored. Here we report a novel "oncogenic" role of XPO5 in advanced prostate cancer. Using prostate cancer models, we found that excess levels of XPO5 override the inhibitory effect of the canoncial miRNA-mRNA regulation, resulting in a global increase in proteins expression. Importantly, we found that decreased expression of XPO5 could promote an increase in proteasome degradation, whereas overexpression of XPO5 leads to altered protein posttranslational modification via hyperglycosylation, resulting in cellular protein stability. We evaluated the therapeutic advantage of targeting XPO5 in prostate cancer and found that knocking down XPO5 in prostate cancer cells suppressed cellular proliferation and tumor development without significantly impacting normal fibroblast cells survival. To our knowledge, this is the first report describing the oncogenic role of XPO5 in overriding the miRNAs regulation control. Furthermore, we believe that these findings will provide an explanation as to why, in some cancers that express higher abundance of mature miRNAs, fail to suppress their potential protein targets.
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Affiliation(s)
- Naseruddin Höti
- Brady Urological Institute, Department of Urology, Johns Hopkins School of Medicine, Baltimore, MD; Department of Pathology, Division of Clinical Chemistry, Johns Hopkins School of Medicine, Baltimore, MD.
| | - Shuang Yang
- Department of Pathology, Division of Clinical Chemistry, Johns Hopkins School of Medicine, Baltimore, MD
| | - Paul Aiyetan
- Department of Pathology, Division of Clinical Chemistry, Johns Hopkins School of Medicine, Baltimore, MD
| | - Binod Kumar
- Brady Urological Institute, Department of Urology, Johns Hopkins School of Medicine, Baltimore, MD
| | - Yingwei Hu
- Department of Pathology, Division of Clinical Chemistry, Johns Hopkins School of Medicine, Baltimore, MD
| | - David Clark
- Department of Pathology, Division of Clinical Chemistry, Johns Hopkins School of Medicine, Baltimore, MD
| | - Arife Unal Eroglu
- Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Punit Shah
- Department of Pathology, Division of Clinical Chemistry, Johns Hopkins School of Medicine, Baltimore, MD
| | - Tamara Johnson
- Brady Urological Institute, Department of Urology, Johns Hopkins School of Medicine, Baltimore, MD
| | - Wasim H Chowdery
- Department of Urology, The University of Texas Health Science Center at San Antonio, San Antonio, TX
| | - Hui Zhang
- Department of Pathology, Division of Clinical Chemistry, Johns Hopkins School of Medicine, Baltimore, MD
| | - Ronald Rodriguez
- Department of Urology, The University of Texas Health Science Center at San Antonio, San Antonio, TX
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Jaeger A, Hadlich F, Kemper N, Lübke-Becker A, Muráni E, Wimmers K, Ponsuksili S. MicroRNA expression profiling of porcine mammary epithelial cells after challenge with Escherichia coli in vitro. BMC Genomics 2017; 18:660. [PMID: 28836962 PMCID: PMC5571640 DOI: 10.1186/s12864-017-4070-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2017] [Accepted: 08/16/2017] [Indexed: 12/14/2022] Open
Abstract
Background Coliform mastitis is a symptom of postpartum dysgalactia syndrome (PDS), a multifactorial infectious disease of sows. Our previous study showed gene expression profile change after bacterial challenge of porcine mammary epithelial cells (PMECs). These mRNA expression changes may be regulated through microRNAs (miRNAs) which play critical roles in biological processes. Therefore, miRNA expression profile was investigated in PMECs. Results PMECs were isolated from three lactating sows and challenged with heat-inactivated potential mastitis-causing pathogen Escherichia coli (E. coli) for 3 h and 24 h, in vitro. At 3 h post-challenge with E. coli, target gene prediction identified a critical role of miRNAs in regulation of host immune responses and homeostasis of PMECs mediated by affecting pathways including cytokine binding (miR-202, miR-3277, miR-4903); IL-10/PPAR signaling (miR-3277, miR-4317, miR-548); and NF-ĸB/TNFR2 signaling (miR-202, miR-2262, miR-885-3p). Target genes of miRNAs in PMECs at 24 h were significantly enriched in pathways associated with interferon signaling (miR-210, miR-23a, miR-1736) and protein ubiquitination (miR-125, miR-128, miR-1280). Conclusions This study provides first large-scale miRNA expression profiles and their predicted target genes in PMECs after contact with a potential mastitis-causing E. coli strain. Both, highly conserved miRNAs known from other species as well as novel miRNAs were identified in PMECs, representing candidate predictive biomarkers for PDS. Time-dependent pathogen clearance suggests an important role of PMECs in inflammatory response of the first cellular barrier of the porcine mammary gland. Electronic supplementary material The online version of this article (doi:10.1186/s12864-017-4070-2) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- A Jaeger
- Institute for Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, D-18196, Dummerstorf, Germany
| | - F Hadlich
- Institute for Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, D-18196, Dummerstorf, Germany
| | - N Kemper
- Institute for Animal Hygiene, Animal Welfare and Farm Animal Behaviour, University of Veterinary Medicine Hannover, Foundation, D-30559, Hannover, Germany
| | - A Lübke-Becker
- Institute of Microbiology and Epizootics, Department of Veterinary Medicine at the Freie Universität Berlin, D-14163, Berlin, Germany
| | - E Muráni
- Institute for Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, D-18196, Dummerstorf, Germany
| | - K Wimmers
- Institute for Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, D-18196, Dummerstorf, Germany
| | - S Ponsuksili
- Institute for Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, D-18196, Dummerstorf, Germany.
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48
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Yuan K, Ai WB, Wan LY, Tan X, Wu JF. The miR-290-295 cluster as multi-faceted players in mouse embryonic stem cells. Cell Biosci 2017; 7:38. [PMID: 28794853 PMCID: PMC5547456 DOI: 10.1186/s13578-017-0166-2] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2017] [Accepted: 08/01/2017] [Indexed: 01/04/2023] Open
Abstract
Increasing evidence indicates that embryonic stem cell specific microRNAs (miRNAs) play an essential role in the early development of embryo. Among them, the miR-290-295 cluster is the most highly expressed in the mouse embryonic stem cells and involved in various biological processes. In this paper, we reviewed the research progress of the function of the miR-290-295 cluster in embryonic stem cells. The miR-290-295 cluster is involved in regulating embryonic stem cell pluripotency maintenance, self-renewal, and reprogramming somatic cells to an embryonic stem cell-like state. Moreover, the miR-290-295 cluster has a latent pro-survival function in embryonic stem cells and involved in tumourigenesis and senescence with a great significance. Elucidating the interaction between the miR-290-295 cluster and other modes of gene regulation will provide us new ideas on the biology of pluripotent stem cells. In the near future, the broad prospects of the miRNA cluster will be shown in the stem cell field, such as altering cell identities with high efficiency through the transient introduction of tissue-specific miRNA cluster.
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Affiliation(s)
- Kai Yuan
- Institute of Organ Fibrosis and Targeted Drug Delivery, Medical College, China Three Gorges University, 8 Daxue Road, Xiling District, Yichang, 443002 China
| | - Wen-Bing Ai
- The Yiling Hospital of Yichang, 31 Donghu Road, Yi Ling District, Yichang, 443100 Hubei China
| | - Lin-Yan Wan
- Institute of Organ Fibrosis and Targeted Drug Delivery, Medical College, China Three Gorges University, 8 Daxue Road, Xiling District, Yichang, 443002 China.,The RenMin Hospital, China Three Gorges University, 31 Huti Subdistrict, Xi Ling District, Yichang, 443000 Hubei China
| | - Xiao Tan
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, 8 Daxue Road, Xiling District, Yichang, 443002 China
| | - Jiang-Feng Wu
- Institute of Organ Fibrosis and Targeted Drug Delivery, Medical College, China Three Gorges University, 8 Daxue Road, Xiling District, Yichang, 443002 China
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49
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Luo ZY, Dai XL, Ran XQ, Cen YX, Niu X, Li S, Huang SH, Wang JF. Identification and profile of microRNAs in Xiang pig testes in four different ages detected by Solexa sequencing. Theriogenology 2017; 117:61-71. [PMID: 28683952 DOI: 10.1016/j.theriogenology.2017.06.023] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2017] [Revised: 06/22/2017] [Accepted: 06/22/2017] [Indexed: 01/07/2023]
Abstract
To further understand the role of microRNA (miRNA) during testicular development, we constructed four small RNA libraries from the testes of the Chinese indigenous Xiang pig at four different ages, which were sequenced using high-throughput Solexa deep sequencing methods. It yielded over 23 million high-quality reads and 1,342,579 unique sequences. At two and three months of age, the proportion which represented miRNAs was the most abundant class of small RNAs, but it was gradually replaced by the category that represented piRNAs in adult testes. We identified 543 known and homologous conserved porcine miRNAs and 49 potential novel miRNAs. There were 306 known miRNAs which were co-expressed in four libraries. Six miRNAs and three potential novel miRNAs were validated in testes and sperms of Xiang pig by RT-qPCR method. Many clusters of mature miRNA variants were observed, in which let-7 family was the most abundant one. After comparison among libraries, 204 miRNAs were identified as being differentially expressed and likely involved in the development and spermatogenesis of pig testes. This work presented a general genome-wide expression profile of the testes-expressed small RNAs in different ages of pig testes. Our results suggested that miRNAs performed a role in the regulation of mRNAs in puberty pig testes while piRNAs likely functioned mainly in sexually mature pig testes.
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Affiliation(s)
- Zhi-Yu Luo
- College of Animal Science, Guizhou University, Guiyang, China
| | - Xin-Lan Dai
- Institute of Agro-Bioengineering, Guizhou University, Guiyang, China
| | - Xue-Qin Ran
- College of Animal Science, Guizhou University, Guiyang, China.
| | - Yong-Xiu Cen
- College of Animal Science, Guizhou University, Guiyang, China
| | - Xi Niu
- Institute of Agro-Bioengineering, Guizhou University, Guiyang, China
| | - Sheng Li
- Institute of Agro-Bioengineering, Guizhou University, Guiyang, China
| | - Shi-Hui Huang
- College of Animal Science, Guizhou University, Guiyang, China
| | - Jia-Fu Wang
- Institute of Agro-Bioengineering, Guizhou University, Guiyang, China; Tongren University, Tongren, China.
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50
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Wu Y, Sun X, Song B, Qiu X, Zhao J. MiR-375/SLC7A11 axis regulates oral squamous cell carcinoma proliferation and invasion. Cancer Med 2017. [PMID: 28627030 PMCID: PMC5504333 DOI: 10.1002/cam4.1110] [Citation(s) in RCA: 96] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
We aimed to detect the functions of miR‐375/SLC7A11 axis on oral squamous cell carcinoma (OSCC) cell proliferation and invasion. Expression levels of miR‐375 and SLC7A11 in OSCC tissues and cells were measured with RT‐qPCR and western blot. Targeting site was predicted by TargetScan and confirmed by dual luciferase reporting assay. By way of manipulating the expression level of miR‐375 and SLC7A11 in CAL‐27 and Tca8113 cell lines, the cell biological abilities were evaluated. MTT, colony formation, Transwell, wound healing assays and flow cytometry were used to detect OSCC cell viability, proliferation, invasion, migration and apoptosis, respectively. MiR‐375 was significantly downregulated in OSCC tissues and cells compared to adjacent tissue and normal oral cell line respectively while SLC7A11 was upregulated. Targeting relationship was verified by luciferase reporting assay, and miR‐375 could effectively suppress SLC7A11 level in OSCC cells. Replenishing of miR‐375 significantly repressed OSCC cell viability, proliferation, invasion and migration and induced cell apoptosis and G1/G0 arrest. Overexpression of SLC7A11 recovered those biological abilities in miR‐375 upregulated cells. Collective data suggested that miR‐375 served as a tumor suppressor via regulating SLC7A11. Replenishing of miR‐375 or knockout of SLC7A11 could be therapeutically exploited.
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Affiliation(s)
- Yadong Wu
- Department of Oral and Maxillofacial Surgery, Stomatological Hospital of Southern Medical University & Guangdong Provincial Stomatological Hospital, Southern Medical University, Guangzhou, 510260, Guangdong, China.,Department of Stomatology, Guizhou Provincial People's Hospital, Guiyang, 550002, Guizhou, China
| | - Xiangjie Sun
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Bin Song
- Department of Stomatology, Guizhou Provincial People's Hospital, Guiyang, 550002, Guizhou, China
| | - Xiaoling Qiu
- Department of Oral and Maxillofacial Surgery, Stomatological Hospital of Southern Medical University & Guangdong Provincial Stomatological Hospital, Southern Medical University, Guangzhou, 510260, Guangdong, China
| | - Jianjiang Zhao
- Department of Oral and Maxillofacial Surgery, Stomatological Hospital of Southern Medical University & Guangdong Provincial Stomatological Hospital, Southern Medical University, Guangzhou, 510260, Guangdong, China
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