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Asghariazar V, Makaremi S, Amani N, Zare E, Kadkhodayi M, Eterafi M, Golmohammadi MG, Safarzadeh E. MicroRNA 320a-3p up-regulation reduces PD-L1 expression in gastric cancer cells: an experimental and bioinformatic study. Sci Rep 2025; 15:8239. [PMID: 40065071 PMCID: PMC11894147 DOI: 10.1038/s41598-025-92537-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Accepted: 02/28/2025] [Indexed: 03/14/2025] Open
Abstract
Growing evidence suggests that dysregulated microRNAs were critical in the development of tumors and the progression number of malignancies. This research aimed to check the effect of microRNA 320a-3p transfection on gastric cancer (GC) cell lines. Following transfection, the efficacy was determined by the RT-PCR method. After that, MTT, scratch assay, DAPI staining, RT-PCR, and flow cytometry were used respectively. The results demonstrated that the viability of GC cells considerably decreased following transfection. Moreover, microRNA 320a-3p transfection significantly suppressed cell migration and induced apoptosis in these cells. We found that transfection of microRNA 320a-3p remarkably decreased PD-L1 gene expression and influenced epithelial-mesenchymal transition (EMT)-related and apoptotic gene expressions. The findings propose that microRNA 320a-3p could decrease cell proliferation and migration and induce apoptosis by increasing TP53 and CASP3 expression levels in GC cells. Notably, microRNA 320a-3p might be a potential target in GC immunotherapy by suppressing the PD-L1 gene expression.
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Affiliation(s)
- Vahid Asghariazar
- Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
- Deputy of Research and Technology, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Shima Makaremi
- Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
- School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Negin Amani
- School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Erfan Zare
- Students Research Committee, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Mahtab Kadkhodayi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Majid Eterafi
- Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
- Students Research Committee, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Mohammad Ghasem Golmohammadi
- Department of Anatomical Sciences and Pathology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Elham Safarzadeh
- Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.
- Department of Microbiology, Parasitology, and Immunology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, 5166614711, Iran.
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Mikulski D, Nowicki M, Dróźdż I, Misiewicz M, Kościelny KP, Okoński K, Krawiec K, Perdas E, Wierzbowska A, Fendler W. High serum miR-223-3p expression level predicts complete response and prolonged overall survival in multiple myeloma patients undergoing autologous hematopoietic stem cell transplantation. Front Oncol 2023; 13:1250355. [PMID: 37829335 PMCID: PMC10565214 DOI: 10.3389/fonc.2023.1250355] [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: 06/30/2023] [Accepted: 08/23/2023] [Indexed: 10/14/2023] Open
Abstract
Introduction AHSCT is the treatment of choice for newly diagnosed patients with transplant-eligible multiple myeloma (MM). However, considerable variability in response to autologous hematopoietic stem cell transplantation (AHSCT) results in only 50% of patients achieving complete response (CR) after AHSCT, which is directly associated with improved progression-free and overall survival (OS). In this study, we aimed to investigate the potential predictive role of selected serum miRNAs in MM patients who underwent AHSCT. Patients and methods Serum expression level of 6 miRNAs: miR-221-3p, miR-15b-5p, miR-223-3p, miR-320c, miR-361-3p, and miR-150-5p was evaluated in 51 patients who underwent AHSCT. Blood samples were collected at two time points: before conditioning chemotherapy (T1) and fourteen days after transplant (+14) (T2). Results All selected miRNAs significantly changed their expression level across the procedure- two were up-regulated after AHSCT: hsa-miR-320c (FC 1.42, p<0.0001) and hsa-miR-361-3p (FC 1.35, p=0.0168); four were down-regulated: hsa-miR-15b-5p (FC 0.53, p<0.0001), hsa-miR-221-3p (FC 0.78, p=0.0004), hsa-miR-223-3p (FC 0.74, p=0.0015) and hsa-miR-150-5p (FC 0.75, p=0.0080). Notably, before AHSCT, hsa-miR-223-3p was down-regulated in International Staging System (ISS) III patients (FC=0.76, p=0.0155), and hsa-miR-320c was up-regulated (FC=1.27, p=0.0470). These differences became non-significant after AHSCT. Eight (15.69%) patients achieved CR before AHSCT and 17 patients (33.33%) at +100 days after AHSCT. In multivariate logistic regression analysis, achievement of CR after induction and hsa-miR-223-3p at T1 were independent predictors of CR after AHSCT. In multivariate Cox regression analysis, hsa-miR-223-3p at T1 expression level was associated with prolonged OS (HR 0.06, 95%CI: 0.00 - 0.99, p=0.0488). Conclusion Serum expression of has-miR-223-3p is a predictor of CR and prolonged OS in MM patients undergoing AHSCT.
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Affiliation(s)
- Damian Mikulski
- Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland
- Department of Hematooncology, Copernicus Memorial Hospital in Lodz, Lodz, Poland
| | - Mateusz Nowicki
- Department of Hematology and Transplantology, Copernicus Memorial Hospital in Lodz, Lodz, Poland
- Department of Hematology, Medical University of Lodz, Lodz, Poland
| | - Izabela Dróźdż
- Department of Clinical Genetics, Medical University of Lodz, Lodz, Poland
| | - Małgorzata Misiewicz
- Department of Hematology and Transplantology, Copernicus Memorial Hospital in Lodz, Lodz, Poland
| | - Kacper Piotr Kościelny
- Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland
| | - Karol Okoński
- Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland
| | - Kinga Krawiec
- Department of Hematology and Transplantology, Copernicus Memorial Hospital in Lodz, Lodz, Poland
- Department of Hematology, Medical University of Lodz, Lodz, Poland
| | - Ewelina Perdas
- Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland
| | - Agnieszka Wierzbowska
- Department of Hematology and Transplantology, Copernicus Memorial Hospital in Lodz, Lodz, Poland
- Department of Hematology, Medical University of Lodz, Lodz, Poland
| | - Wojciech Fendler
- Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland
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Yan T, Wang X, Zhou D, Qiu H, Zhang J, Yang W. Circ_0003489 facilitates multiple myeloma progression by targeting miR-433-3p/PBX3 axis. HEMATOLOGY (AMSTERDAM, NETHERLANDS) 2022; 27:951-959. [PMID: 36004524 DOI: 10.1080/16078454.2022.2109554] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
BACKGROUND Multiple myeloma (MM) is a relatively common hematologic tumor, and the study of non-coding RNAs in MM is gradually increasing. Our study aimed to reveal the regulatory mechanism of circular RNA_0003489 (circ_0003489)/microRNA-433-3p (miR-433-3p)/Pre-B-cell leukemia homeobox 3 (PBX3) axis in MM. METHODS Circ_0003489, miR-433-3p and PBX3 contents were measured by real-time quantitative PCR or western blot. Functionally, MM cell proliferation and apoptosis were evaluated using cell counting kit-8, flow cytometry and EdU assays. Interaction between miR-433-3p and circ_0003489 or PBX3 was confirmed with the application of dual-luciferase reporter assay and RNA pull down assay. RESULTS Circ_0003489 and PBX3 were upregulated, while miR-433-3p was downregulated in MM tissues. Circ_0003489 knockdown or miR-433-3p overexpression remarkably suppressed MM proliferation and increased apoptosis in vitro. In terms of mechanism, circ_0003489 could sponge miR-433-3p to regulate PBX3. Besides, miR-433-3p downregulation or PBX3 overexpression reversed the inhibition effect of circ_0003489 knockdown on MM progression. CONCLUSION Circ_0003489 facilitated MM progression by targeting miR-433-3p/PBX3 axis, suggesting that it might be a potential target for MM.
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Affiliation(s)
- Tielun Yan
- Department of Clinical Laboratory, Lishui Second People's Hospital, Lishui, People's Republic of China
| | - Xiaoli Wang
- Department of Hematology, Lishui People's Hospital, Lishui, People's Republic of China
| | - Dajin Zhou
- Department of Clinical Laboratory, Lishui Second People's Hospital, Lishui, People's Republic of China
| | - Haibo Qiu
- Clinical Laboratory Center, Lishui People's Hospital, Lishui, People's Republic of China
| | - Jiliang Zhang
- Clinical Laboratory Center, Lishui People's Hospital, Lishui, People's Republic of China
| | - Weixiong Yang
- Department of Hematology, Lishui People's Hospital, Lishui, People's Republic of China
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Hatmal MM, Al-Hatamleh MAI, Olaimat AN, Alshaer W, Hasan H, Albakri KA, Alkhafaji E, Issa NN, Al-Holy MA, Abderrahman SM, Abdallah AM, Mohamud R. Immunomodulatory Properties of Human Breast Milk: MicroRNA Contents and Potential Epigenetic Effects. Biomedicines 2022; 10:1219. [PMID: 35740242 PMCID: PMC9219990 DOI: 10.3390/biomedicines10061219] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Revised: 05/15/2022] [Accepted: 05/17/2022] [Indexed: 02/07/2023] Open
Abstract
Infants who are exclusively breastfed in the first six months of age receive adequate nutrients, achieving optimal immune protection and growth. In addition to the known nutritional components of human breast milk (HBM), i.e., water, carbohydrates, fats and proteins, it is also a rich source of microRNAs, which impact epigenetic mechanisms. This comprehensive work presents an up-to-date overview of the immunomodulatory constituents of HBM, highlighting its content of circulating microRNAs. The epigenetic effects of HBM are discussed, especially those regulated by miRNAs. HBM contains more than 1400 microRNAs. The majority of these microRNAs originate from the lactating gland and are based on the remodeling of cells in the gland during breastfeeding. These miRNAs can affect epigenetic patterns by several mechanisms, including DNA methylation, histone modifications and RNA regulation, which could ultimately result in alterations in gene expressions. Therefore, the unique microRNA profile of HBM, including exosomal microRNAs, is implicated in the regulation of the genes responsible for a variety of immunological and physiological functions, such as FTO, INS, IGF1, NRF2, GLUT1 and FOXP3 genes. Hence, studying the HBM miRNA composition is important for improving the nutritional approaches for pregnancy and infant's early life and preventing diseases that could occur in the future. Interestingly, the composition of miRNAs in HBM is affected by multiple factors, including diet, environmental and genetic factors.
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Affiliation(s)
- Ma’mon M. Hatmal
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan;
| | - Mohammad A. I. Al-Hatamleh
- Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kota Bharu 16150, Malaysia;
| | - Amin N. Olaimat
- Department of Clinical Nutrition and Dietetics, Faculty of Applied Medical Sciences, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan; (A.N.O.); (M.A.A.-H.)
| | - Walhan Alshaer
- Cell Therapy Center (CTC), The University of Jordan, Amman 11942, Jordan;
| | - Hanan Hasan
- Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan;
| | - Khaled A. Albakri
- Faculty of Medicine, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan;
| | - Enas Alkhafaji
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of Jordan, Amman 11942, Jordan;
| | - Nada N. Issa
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan;
| | - Murad A. Al-Holy
- Department of Clinical Nutrition and Dietetics, Faculty of Applied Medical Sciences, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan; (A.N.O.); (M.A.A.-H.)
| | - Salim M. Abderrahman
- Department of Biology and Biotechnology, Faculty of Sciences, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan;
| | - Atiyeh M. Abdallah
- Department of Biomedical Sciences, College of Health Sciences, QU Health, Qatar University, Doha 2713, Qatar;
| | - Rohimah Mohamud
- Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kota Bharu 16150, Malaysia;
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Bi X, Jiang Z, Luan Z, Qiu D. Crocin exerts anti-proliferative and apoptotic effects on cutaneous squamous cell carcinoma via miR-320a/ATG2B. Bioengineered 2021; 12:4569-4580. [PMID: 34320900 PMCID: PMC8806488 DOI: 10.1080/21655979.2021.1955175] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Accepted: 07/08/2021] [Indexed: 11/06/2022] Open
Abstract
Cutaneous squamous cell carcinoma (cSCC) is a highly prevalent skin malignancy, and the effective therapy still remains a challenge. Crocin can be used for cSCC therapy. This study explored the effects of cSCC cells treatment with crocin in vitro and in vivo. The study used A431 and SCL-1 cells lines, cSCC human samples and BALB/C nude mice for investigations. Apoptosis was determined by MTT assays, while miR-320a and ATG2B expressions were validated through RT-qPCR. Interaction of miR-320a with ATG2B was examined via dual luciferase reporter assay. The autophagy and apoptosis proteins expressions were further confirmed through western blot and immunofluorescence staining assays. The results indicated a significantly upregulated miR-320a, but a down-regulated ATG2B expression in the cSCC clinical samples. Crocin significantly repressed cSCC cells growth, and induced apoptosis through autophagy. Furthermore, miR-320a expression was inhibited and ATG2B expression was increased. Dual luciferase reporter assay revealed that miR-320a regulated ATG2B expression directly. Additionally, the upregulation of ATG2B expression in cSCC cells inhibited cell proliferation and led to cell apoptosis. Crocin also reduced tumor growth and stimulated the apoptosis in vivo. In conclusion, miR-320a is upregulated and ATG2B is down-regulated in cSCC, Crocin suppresses the proliferation and induces apoptosis of cSCC cells. Further, Crocin increases autophagy while miR-320a hinders autophagy and the apoptotic effects of crocin on cSCC cells. MiR-320a binds ATG2B directly, and ATG2B expression is upregulated by crocin. Finally, Crocin triggers cSCC cells apoptosis in vivo. Crocin can target ATG2B/miR-320a and may be an effective alternative for cSCC treatment.
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Affiliation(s)
- Xiaoqing Bi
- Department of Dermatology, Zibo Central Hospital, Zibo, China
| | - Zhenjuan Jiang
- Department of Gynecology, Affiliated Qingdao Central Hospital, Qingdao University, Qingdao, China
| | - Zhaohui Luan
- Department of Gynecology, Affiliated Qingdao Central Hospital, Qingdao University, Qingdao, China
| | - Daoqing Qiu
- Department of Dermatology, Zibo Central Hospital, Zibo, China
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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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Liang Y, Li S, Tang L. MicroRNA 320, an Anti-Oncogene Target miRNA for Cancer Therapy. Biomedicines 2021; 9:biomedicines9060591. [PMID: 34071109 PMCID: PMC8224659 DOI: 10.3390/biomedicines9060591] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 05/18/2021] [Accepted: 05/20/2021] [Indexed: 12/11/2022] Open
Abstract
MicroRNAs are a set of highly conserved non-coding RNAs that control gene expression at the post-transcriptional/translational levels by binding to the 3′-UTR of diverse target genes. Increasing evidence indicates that miRNAs not only play a vital role in many biological processes, but they are also frequently deregulated in pathological conditions, including cancer. The miR-320 family is one of many tumor suppressor families and is composed of five members, which has been demonstrated to be related to the repression of epithelial-mesenchymal transition (EMT) inhibition, cell proliferation, and apoptosis. Moreover, this family has been shown to regulate drug resistance, and act as a potential biomarker for the diagnosis, prognosis, and prediction of cancer. In this review, we summarized recent research with reference to the tumor suppressor function of miR-320 and the regulation mechanisms of miR-320 expression. The collected evidence shown here supports that miR-320 may act as a novel biomarker for cancer prognosis and therapeutic response to cancer treatment.
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Affiliation(s)
- Yuanyuan Liang
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China;
| | - Shun Li
- Department of Immunology, School of Basic Medical Sciences, Chengdu Medical College, Chengdu 610500, China
- Non-Coding RNA and Drug Discovery Key Laboratory of Sichuan Province, Chengdu Medical College, Chengdu 610500, China
- Correspondence: (S.L.); (L.T.)
| | - Liling Tang
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China;
- Correspondence: (S.L.); (L.T.)
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Hao X, Xin R, Dong W. Decreased serum exosomal miR-320a expression is an unfavorable prognostic factor in patients with hepatocellular carcinoma. J Int Med Res 2021; 48:300060519896144. [PMID: 32339037 PMCID: PMC7218457 DOI: 10.1177/0300060519896144] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Objective Circulating microRNAs (miRNAs) have promising potential as diagnostic or prognostic biomarkers for hepatocellular carcinoma (HCC). This study aimed to analyze the clinical significance of serum exosomal miR-320a expression in patients with HCC. Methods A total of 104 patients with HCC, 55 patients with chronic liver disease (CLD), and 50 healthy volunteers were enrolled. Serum exosomal miR-320a levels were measured by quantitative reverse-transcriptase polymerase chain reaction and compared among the groups. The relationships between exosomal miR-320a levels and clinicopathological factors in patients with HCC were also analyzed. Results Serum exosomal miR-320a levels were significantly lower in patients with HCC compared with patients with CLD and healthy controls. Receiver-operating characteristic curve analysis showed that serum exosomal miR-320a had good diagnostic value for distinguishing between HCC subjects and normal controls. Serum exosomal miR-320a levels were significantly elevated 1 month after surgery in patients with HCC. Moreover, serum exosomal miR-320a downregulation was strongly associated with positive lymph node metastasis, positive vein invasion, advanced TNM stage, and shorter survival. Serum exosomal miR-320a was confirmed as an independent prognostic marker for HCC. Conclusions Collectively, these results indicate that serum exosomal miR-320a might be a potential biomarker for the detection and prognosis of HCC.
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Affiliation(s)
- Xinjie Hao
- Department of Traditional Chinese Medicine, Qingdao No.6 People's Hospital, Qingdao, Shandong Province, China
| | - Ruopei Xin
- Department of Traditional Chinese Medicine, Qingdao No.6 People's Hospital, Qingdao, Shandong Province, China
| | - Wenjing Dong
- Department of Traditional Chinese Medicine, Qingdao No.6 People's Hospital, Qingdao, Shandong Province, China
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9
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Identification of miR-320 family members as potential diagnostic and prognostic biomarkers in myelodysplastic syndromes. Sci Rep 2021; 11:183. [PMID: 33420276 PMCID: PMC7794569 DOI: 10.1038/s41598-020-80571-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Accepted: 12/23/2020] [Indexed: 12/15/2022] Open
Abstract
Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis and the abnormal differentiation of hematopoietic stem cells. An increasing number of researches have demonstrated that microRNAs play crucial roles in the pathogenesis of myelodysplastic syndromes. Herein, we aimed to identify novel potential microRNAs bound up with the diagnosis and prognosis of MDS. MiRNA microarray analysis was used to screen deregulated microRNAs in the bone marrow of MDS patients. qRT-PCR was employed to confirm the microarray results. All members of miR-320 family (miR-320a, miR-320b, miR-320c, miR-320d, and miR-320e) were significantly increased in MDS patients compared to normal control. Although we found no correlation between miR-320 family and most clinical characteristics, high miR-320c and miR-320d expression seemed to be associated with high numbers of bone marrow (BM) blasts and worse karyotype. High expression of all the members of the miR-320 family seemed to be associated with a high prognostic score based on International Prognostic Scoring System (IPSS). The areas under the miR-320 family member ROC curves were 0.9037 (P < 0.0001), 0.7515 (P = 0.0002), 0.9647 (P < 0.0001), 0.8064 (P < 0.0001) and 0.9019 (P < 0.0001). Regarding Kaplan-Meier analysis, high miR-320c and miR-320d expression were related to shorter overall survival (OS). Moreover, multivariate analysis revealed the independent prognostic value of miR-320d for OS in MDS. The expression of miR-320 family members was up-regulated in MDS, and miR-320 family members could serve as candidate diagnostic biomarkers for MDS. High expression of miR-320d was an independent prognostic factor for OS in MDS.
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Reza AMMT, Yuan YG. microRNAs Mediated Regulation of the Ribosomal Proteins and its Consequences on the Global Translation of Proteins. Cells 2021; 10:110. [PMID: 33435549 PMCID: PMC7827472 DOI: 10.3390/cells10010110] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Accepted: 12/14/2020] [Indexed: 12/23/2022] Open
Abstract
Ribosomal proteins (RPs) are mostly derived from the energy-consuming enzyme families such as ATP-dependent RNA helicases, AAA-ATPases, GTPases and kinases, and are important structural components of the ribosome, which is a supramolecular ribonucleoprotein complex, composed of Ribosomal RNA (rRNA) and RPs, coordinates the translation and synthesis of proteins with the help of transfer RNA (tRNA) and other factors. Not all RPs are indispensable; in other words, the ribosome could be functional and could continue the translation of proteins instead of lacking in some of the RPs. However, the lack of many RPs could result in severe defects in the biogenesis of ribosomes, which could directly influence the overall translation processes and global expression of the proteins leading to the emergence of different diseases including cancer. While microRNAs (miRNAs) are small non-coding RNAs and one of the potent regulators of the post-transcriptional gene expression, miRNAs regulate gene expression by targeting the 3' untranslated region and/or coding region of the messenger RNAs (mRNAs), and by interacting with the 5' untranslated region, and eventually finetune the expression of approximately one-third of all mammalian genes. Herein, we highlighted the significance of miRNAs mediated regulation of RPs coding mRNAs in the global protein translation.
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Affiliation(s)
- Abu Musa Md Talimur Reza
- Jiangsu Co-Innovation Center of Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China;
- Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland
| | - Yu-Guo Yuan
- Jiangsu Co-Innovation Center of Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China;
- Jiangsu Key Laboratory of Zoonosis/Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou 225009, China
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11
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P53-regulated miR-320a targets PDL1 and is downregulated in malignant mesothelioma. Cell Death Dis 2020; 11:748. [PMID: 32929059 PMCID: PMC7490273 DOI: 10.1038/s41419-020-02940-w] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 07/09/2020] [Accepted: 07/09/2020] [Indexed: 02/07/2023]
Abstract
Malignant pleural mesothelioma (MPM) is an aggressive cancer, related to asbestos exposure, which has a dismal prognosis. MPM diagnosis is late and often challenging, suggesting the need to identify more reliable molecular biomarkers. Here, we set out to identify differentially expressed miRNAs in epithelioid, biphasic, and sarcomatoid MPMs versus normal mesothelium and explored specific miRNA contribution to mesothelial tumorigenesis. We screened an LNA™-based miRNA-microrray with 14 formalin-fixed paraffin-embedded (FFPE) MPMs and 6 normal controls. Through real-time qRT-PCR we extended the analysis of a miRNA subset and further investigated miR-320a role through state-of-the-art techniques. We identified 16 upregulated and 32 downregulated miRNAs in MPMs versus normal tissue, including the previously identified potential biomarkers miR-21, miR-126, miR-143, miR-145. We showed in an extended series that miR-145, miR-10b, and miR-320a levels can discriminate tumor versus controls with high specificity and sensitivity. We focused on miR-320a because other family members were found downregulated in MPMs. However, stable miR-320a ectopic expression induced higher proliferation and migration ability, whereas miR-320a silencing reduced these processes, not supporting a classic tumor-suppressor role in MPM cell lines. Among putative targets, we found that miR-320a binds the 3'-UTR of the immune inhibitory receptor ligand PDL1 and, consistently, miR-320a modulation affects PDL1 levels in MPM cells. Finally, we showed that p53 over-expression induces the upregulation of miR-320a, along with miR-200a and miR-34a, both known to target PDL1, and reduces PDL1 levels in MPM cells. Our data suggest that PDL1 expression might be due to a defective p53-regulated miRNA response, which could contribute to MPM immune evasion or tumorigenesis through tumor-intrinsic roles.
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12
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Morgan R, Pandha HS. PBX3 in Cancer. Cancers (Basel) 2020; 12:cancers12020431. [PMID: 32069812 PMCID: PMC7072649 DOI: 10.3390/cancers12020431] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Revised: 02/04/2020] [Accepted: 02/06/2020] [Indexed: 12/11/2022] Open
Abstract
PBX3 is a homeodomain-containing transcription factor of the pre-B cell leukemia (PBX) family, members of which have extensive roles in early development and some adult processes. A number of features distinguish PBX3 from other PBX proteins, including the ability to form specific and stable interactions with DNA in the absence of cofactors. PBX3 has frequently been reported as having a role in the development and maintenance of a malignant phenotype, and high levels of PBX3 tumor expression have been linked to shorter overall survival in cancer. In this review we consider the similarities and differences in the function of PBX3 in different cancer types and draw together the core signaling pathways involved to help provide a better insight into its potential as a therapeutic target.
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Affiliation(s)
- Richard Morgan
- Institute of Cancer Therapeutics, Faculty of Life Sciences, University of Bradford, Bradford BD7 1DP, UK
- Correspondence: ; Tel.: +44-1274-233225; Fax: +44-1274-233234
| | - Hardev S Pandha
- Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UK;
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13
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PBX3 Promotes Tumor Growth and Angiogenesis via Activation of AT1R/VEGFR2 Pathway in Papillary Thyroid Carcinoma. BIOMED RESEARCH INTERNATIONAL 2020; 2020:8954513. [PMID: 32047817 PMCID: PMC7007751 DOI: 10.1155/2020/8954513] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/19/2019] [Revised: 07/20/2019] [Accepted: 07/29/2019] [Indexed: 11/17/2022]
Abstract
PBX3 (Pre-B-cell leukemia homeobox 3) had been considered to be a multifunctional oncogene which involved in tumor growth, invasion, and metastasis in leukemia and some solid tumors. However, the contribution of PBX3 to papillary thyroid carcinoma (PTC) remains unclear. In this study, we found that PBX3 expression was significantly upregulated in PTC tissues compared to adjacent normal tissues, and high levels of PBX3 were correlated with tumor size, lymphatic metastasis, TMN stage, and poor prognosis of PTC patients. Overexpression of PBX3 in PTC cell lines promoted cell proliferation. Consistently, knockdown of PBX3 by shRNA induced cell cycle arrest at G0/G1 phase, and inhibited angiogenesis and tumor growth in vitro and in vivo. Furthermore, PBX3 promoted PTC cell proliferation and angiogenesis through activation of AT1R/VEGFR2 pathway while overexpression of AT1R and treatment with VEGFA reversed PBX3-shRNA-induced decreased phosphorylation of VEGFR2 and its downstream (ERK1/2, AKT and Src). It demonstrated that PBX3 could be used as a potential prognostic biomarker and therapeutic target for PTC.
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14
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The novel circCLK3/miR-320a/FoxM1 axis promotes cervical cancer progression. Cell Death Dis 2019; 10:950. [PMID: 31831728 PMCID: PMC6908646 DOI: 10.1038/s41419-019-2183-z] [Citation(s) in RCA: 73] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Revised: 11/28/2019] [Accepted: 11/29/2019] [Indexed: 12/18/2022]
Abstract
As a new class of non-coding RNA, circular RNAs (circRNAs) play crucial roles in the development and progression of various cancers. However, the detailed functions of circRNAs in cervical cancer have seldom been reported. In this study, circRNA sequence was applied to detect the differentially expressed circRNAs between cervical cancer tissues and adjacent normal tissues. The relationships between circCLK3 level with clinicopathological characteristics and prognosis were analyzed. In vitro CCK-8, cell count, cell colony, cell wound healing, transwell migration and invasion, and in vivo tumorigenesis and lung metastasis models were performed to evaluate the functions of circCLK3. The pull-down, RNA immunoprecipitation (RIP), luciferase reporter and rescue assays were employed to clarify the interaction between circCLK3 and miR-320a and the regulation of miR-320a on FoxM1. We found that the level of circCLK3 was remarkably higher in cervical cancer tissues than in adjacent normal tissues, and closely associated with tumor differentiation, FIGO stage and depth of stromal invasion. Down-regulated circCLK3 evidently inhibited cell growth and metastasis of cervical cancer in vitro and in vivo, while up-regulated circCLK3 significantly promoted cell growth and metastasis in vitro and in vivo. The pull-down, luciferase reporter and RIP assays demonstrated that circCLK3 directly bound to and sponge miR-320a. MiR-320a suppressed the expression of FoxM1 through directly binding to 3′UTR of FoxM1 mRNA. In addition, FoxM1 promoted cell proliferation, migration, and invasion of cervical cancer, while miR-320a suppressed cell proliferation, migration, and invasion through suppressing FoxM1, and circCLK3 enhanced cell proliferation, migration and invasion through sponging miR-320a and promoting FoxM1 expression. In summary, circCLK3 may serve as a novel diagnostic biomarker for disease progression and a promising molecular target for early diagnoses and treatments of cervical cancer.
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15
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Liang H, Tang Y, Zhang H, Zhang C. MiR-32-5p Regulates Radiosensitization, Migration And Invasion Of Colorectal Cancer Cells By Targeting TOB1 Gene. Onco Targets Ther 2019; 12:9651-9661. [PMID: 31814731 PMCID: PMC6861524 DOI: 10.2147/ott.s228995] [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: 08/28/2019] [Accepted: 10/29/2019] [Indexed: 12/13/2022] Open
Abstract
Background MicroRNAs (miRNAs) play key roles in the development and progression of various cancers. However, the precise functions and regulation mechanisms of miRNAs in human tumors remain elusive. Methods Quantitative real time-PCR (qRT-PCR) was performed to detect the level of miR-32-5p in colorectal cancer tissues. The relationships between miR-32-5p level with clinicopathological characteristics and prognosis were analyzed. The miR-32-5p inhibitor was employed to knock down the expression of miR-32-5p. The overexpression plasmid and si-RNA targeting TOB1 were generated. Clone formation assays under radiant exposure were used to evaluate the radiosensitization. Transwell migration and invasion were employed to test the ability of cell migration and invasion. Luciferase reporter assays were used to confirm the regulation of miR-32-5p on the expression of TOB1. Rescue experiments were conducted to investigate the effects of TOB1 on the functions of miR-32-5p. Results In this study, we found that miR-32-5p was significantly upregulated in colorectal cancer tissues compared with adjacent normal tissues. The level of miR-32-5p was positively correlated with tumor differentiation and metastasis. Log-rank tests showed that high level of miR-32-5p was significantly correlated with poor overall survival and disease-free survival. Anti-miR-32-5p remarkably enhanced the radiosensitivity and inhibited migration and invasion of colorectal cancer cells. In addition, overexpression of TOB1 obviously increased the radiosensitivity and inhibited migration and invasion of colorectal cancer cells. Moreover, bioinformatics analysis and luciferase reporter assays demonstrated that miR-32-5p suppressed the expression of TOB1 through directly binding to the 3ʹ-UTR of TOB1 mRNA. Rescue experiments indicated that miR-32-5p regulated the radiosensitivity, migration and invasion of colorectal cancer cells through inhibiting TOB1 expression. Conclusion This study suggested that miR-32-5p may serve as a prognostic and therapeutic target for colorectal cancer, and downregulation of miR-32-5p enhanced the radiosensitivity and inhibited migration and invasion through promoting TOB1 expression.
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Affiliation(s)
- Hong Liang
- Department of Gastrointestinal Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan 450003, People's Republic of China
| | - Yumei Tang
- Department of Gastrointestinal Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan 450003, People's Republic of China
| | - Hui Zhang
- Department of Gastrointestinal Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan 450003, People's Republic of China
| | - Chao Zhang
- Department of Gastrointestinal Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan 450003, People's Republic of China
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16
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Li YS, Zou Y, Dai DQ. MicroRNA-320a suppresses tumor progression by targeting PBX3 in gastric cancer and is downregulated by DNA methylation. World J Gastrointest Oncol 2019; 11:842-856. [PMID: 31662823 PMCID: PMC6815930 DOI: 10.4251/wjgo.v11.i10.842] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Revised: 06/19/2019] [Accepted: 07/28/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Ectopic expression of miRNAs promotes tumor development and progression. miRNA (miR)-320a is downregulated in many cancers, including gastric cancer (GC). However, the mechanism underlying its downregulation and the role of miR-320a in GC are unknown.
AIM To determine expression and biological functions of miR-320a in GC and investigate the underlying molecular mechanisms.
METHODS Quantitative real-time polymerase chain reaction (PCR) was used to determine expression of miR-320a in GC cell lines and tissues. TargetScanHuman7.1, miRDB, and microRNA.org were used to predict the possible targets of miR-320a, and a dual luciferase assay was used to confirm the findings. Western blotting was used to detect the protein levels of pre-B-cell leukemia homeobox 3 (PBX3) in GC cells and tissue samples. Cell Counting Kit-8 proliferation, Transwell, wound healing, and apoptosis assays were performed to analyze the biological functions of miR-320a in GC cells. Methylation-specific PCR was used to analyze the methylation level of the miR-320a promoter CpG islands. 5-Aza-2’-deoxycytidine (5-Aza-CdR) and trichostatin A (TSA) were used to treat GC cells.
RESULTS miR-320a expression was lower in GC cell lines and tissues than in the normal gastric mucosa cell line GES-1 and matched adjacent normal tissues. miR-320a overexpression suppressed GC cell proliferation, invasion and migration, and induced apoptosis. PBX3 was a target of miR-320a in GC. The methylation level of the miR-320a promoter CpG islands was elevated and this was partly reversed by 5-Aza-CdR and TSA.
CONCLUSION miR-320a acts as a tumor suppressor and inhibits malignant behavior of GC cells, partly by targeting PBX3. DNA methylation is an important mechanism associated with low expression of miR-320a.
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Affiliation(s)
- Yong-Shuang Li
- Department of Gastrointestinal Surgery, the Fourth Affiliated Hospital of China Medical University, Shenyang 110032, Liaoning Province, China
| | - Ying Zou
- Department of Gastrointestinal Surgery, the Fourth Affiliated Hospital of China Medical University, Shenyang 110032, Liaoning Province, China
| | - Dong-Qiu Dai
- Department of Gastrointestinal Surgery, the Fourth Affiliated Hospital of China Medical University, Shenyang 110032, Liaoning Province, China
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17
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Mohammad RM, Li Y, Muqbil I, Aboukameel A, Senapedis W, Baloglu E, Landesman Y, Philip PA, Azmi AS. Targeting Rho GTPase effector p21 activated kinase 4 (PAK4) suppresses p-Bad-microRNA drug resistance axis leading to inhibition of pancreatic ductal adenocarcinoma proliferation. Small GTPases 2019; 10:367-377. [PMID: 28641032 PMCID: PMC6748371 DOI: 10.1080/21541248.2017.1329694] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2017] [Revised: 05/08/2017] [Accepted: 05/09/2017] [Indexed: 12/21/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and therapy resistant malignancy. Mutant K-Ras, found in >90% of refractory PDAC, acts as a molecular switch activating Rho GTPase signaling that in turn promotes a plethora of pro-survival molecules and oncogenic microRNAs. We investigated the impact of Rho GTPase effector protein p21 activated kinase 4 (PAK4) inhibition on pro-survival p-Bad and oncogenic miRNA signaling. We demonstrate that the dual NAMPT and PAK4 modulators (KPT-9274 and KPT-9307) inhibit PDAC cell proliferation through downregulation of Bad phosphorylation and upregulation of tumor suppressive miRNAs (miR-145, let-7c, let-7d, miR-34c, miR320 and miR-100). These results suggest that targeting PAK4 could become a promising approach to restore pro-apoptotic function of Bad and simultaneously activate tumor suppressive miRNAs in therapy resistant PDAC.
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Affiliation(s)
- Ramzi M. Mohammad
- Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA
| | - Yiwei Li
- Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA
| | - Irfana Muqbil
- Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA
| | - Amro Aboukameel
- Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA
| | | | | | | | - Philip A. Philip
- Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA
| | - Asfar S. Azmi
- Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA
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18
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Kong Y, Nie ZK, Li F, Guo HM, Yang XL, Ding SF. MiR-320a was highly expressed in postmenopausal osteoporosis and acts as a negative regulator in MC3T3E1 cells by reducing MAP9 and inhibiting PI3K/AKT signaling pathway. Exp Mol Pathol 2019; 110:104282. [PMID: 31301305 DOI: 10.1016/j.yexmp.2019.104282] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Revised: 07/05/2019] [Accepted: 07/09/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Postmenopausal osteoporosis (PMO), as a frequent disease in postmenopausal women, is mainly caused by the lack of estrogen. MiR-320a has been found to abate osteoblast function and induce oxidative stress before osteoporosis. However, studies on the downstream target gene and related signaling pathway of miR-320a in PMO are still obscure. This study aims to deal with these problems. METHODS The expression levels of miR-320a and microtubule-associated protein 9 (MAP9) in patients with osteoporosis were analyzed on the basis of the GEO database. The cells viability was determined by methylthiazolyl tetrazolium bromide (MTT). Flow cytometry and western blot were used to detect the cells apoptosis and the expression of apoptosis-related proteins, respectively. The cells differentiation-related proteins were detected by qRT-PCR and western blot. The interaction between miR-320a and MAP9 was predicted by biological software and verified by dual luciferase reporter assay and rescue assay. The expression levels of PI3K, p-PI3K, AKT and p-AKT in MC3T3-E1 cells were assessed by western blot. RESULTS We observed that miR-320a was over-expressed in PMO patients and exhibited inhibitory effects on MC3T3-E1 cells activity and differentiation, as well as promoting effects on MC3T3-E1 cells apoptosis. MAP9 was verified as a target gene of miR-320a and was negatively regulated by miR-320a. Based on the GEO database, MAP9 was found to be lower expressed in PMO patients. Rescue assay demonstrated that down-regulation of MAP9 could alleviate the promoting effects of miR-320a inhibitor on MC3T3-E1 cells activity and differentiation and the inhibitory effects of miR-320a inhibitor on MC3T3-E1 cells apoptosis. Mechanically, miR-320a/MAP9 possibly took part in MC3T3-E1 cells viability, differentiation and apoptosis via mediating PI3K/AKT signaling pathway. CONCLUSIONS Our outcomes demonstrated that miR-320a promoted MC3T3-E1 cells apoptosis, suppressed MC3T3-E1 cells viability and differentiation through targeting MAP9 and modulating PI3K/AKT signaling pathway, which provided theoretical support for miR-320a/MAP9 as promising targets for the treatment and prevention of PMO.
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Affiliation(s)
- Yao Kong
- Department of Osteoarticular Surgery, Jining NO.1 People's Hospital, China
| | - Zhi-Kui Nie
- Department of Osteoarticular Surgery, Jining NO.1 People's Hospital, China
| | - Feng Li
- Department of Endocrinology, Jining NO.1 People's Hospital, China
| | - Hong-Min Guo
- Department of Osteoarticular Surgery, Jining NO.1 People's Hospital, China
| | - Xing-Lin Yang
- Department of Endocrinology, Jining NO.1 People's Hospital, China
| | - Shao-Feng Ding
- Department of Endocrinology, Jining NO.1 People's Hospital, China.
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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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20
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Identification of protein arginine methyltransferase 7 (PRMT7) inhibitor by virtual screening and biological evaluation in vitro. Med Chem Res 2018. [DOI: 10.1007/s00044-018-2270-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
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21
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Kashyap D, Tuli HS, Garg VK, Goel N, Bishayee A. Oncogenic and Tumor-Suppressive Roles of MicroRNAs with Special Reference to Apoptosis: Molecular Mechanisms and Therapeutic Potential. Mol Diagn Ther 2018; 22:179-201. [PMID: 29388067 DOI: 10.1007/s40291-018-0316-1] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
MicroRNAs (miRNAs) are the non-coding class of minute RNA molecules that negatively control post-transcriptional regulation of various functional genes. These miRNAs are transcribed from the loci present in the introns of functional or protein-coding genes, exons of non-coding genes, or even in the 3'-untranslated region (3'-UTR). They have potential to modulate the stability or translational efficiency of a variety of target RNA [messenger RNA (mRNA)]. The regulatory function of miRNAs has been elucidated in several pathological conditions, including neurological (Alzheimer's disease and Parkinson's disease) and cardiovascular conditions, along with cancer. Importantly, miRNA identification in cancer progression and invasion has evolved as an incipient era in cancer treatment. Several studies have shown the influence of miRNAs on various cancer processes, including apoptosis, invasion, metastasis and angiogenesis. In particular, apoptosis induction in tumor cells through miRNA has been extensively studied. The biphasic mode (up- and down-regulation) of miRNA expression in apoptosis and other cancer processes has already been determined. The findings of these studies could be utilized to develop potential therapeutic strategies for the management of various cancers. The present review critically describes the oncogenic and tumor suppressor role of miRNAs in apoptosis and other cancer processes, therapy resistance, and use of their presence in the body fluids as biomarkers.
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Affiliation(s)
- Dharambir Kashyap
- Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, Punjab, India
| | - Hardeep Singh Tuli
- Department of Biotechnology, Maharishi Markandeshwar University, Mullana-Ambala, 133207, Haryana, India.
| | - Vivek Kumar Garg
- Department of Biochemistry, Government Medical College and Hospital, Chandigarh, 160030, Punjab, India
| | - Neelam Goel
- Department of Information Technology, University Institute of Engineering and Technology, Panjab University, Chandigarh, 160014, Punjab, India
| | - Anupam Bishayee
- Department of Pharmaceutical Sciences, College of Pharmacy, Larkin University, Miami, FL, 33169, USA.
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22
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Zhao S, Wang Y, Lou Y, Wang Y, Sun J, Luo M, Li W, Miao L. MicroRNA‑320a suppresses tumour cell proliferation and invasion of renal cancer cells by targeting FoxM1. Oncol Rep 2018; 40:1917-1926. [PMID: 30066895 PMCID: PMC6111456 DOI: 10.3892/or.2018.6597] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2018] [Accepted: 07/17/2018] [Indexed: 12/20/2022] Open
Abstract
An increasing body of evidence has indicated that microRNAs (miRNAs/miRs) may play an important role in tumourigenesis and tumour progression. Recent studies have demonstrated that miR‑320a is aberrantly expressed in a variety of different types of human cancer. The results of the present study confirmed that the expression of miR‑320a was decreased in clinical specimens and cell lines. Expression of miR‑320a inhibited the growth and invasive ability of ACHN and Caki‑1 cells. Bioinformatics analysis and a luciferase reporter assay demonstrated that forkhead box protein M1 (FoxM1) was directly regulated by miR‑320a. Rescue experiments in vitro revealed that the upregulation of FoxM1 antagonized the miR‑320a‑mediated malignant phenotype in renal cancer. Furthermore, experiments employing a xenograft mouse model revealed that the upregulation of miR‑320a inhibited the proliferation of renal cancer cells in nude mice when FoxM1 protein expression was reduced. Collectively, the present study demonstrated a novel molecular interaction regulated by miR‑320a, which may provide a novel insight into the treatments for renal cancer.
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Affiliation(s)
- Shiyue Zhao
- Department of Nephrology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China
| | - Yangwei Wang
- Department of Nephrology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China
| | - Yan Lou
- Department of Nephrology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China
| | - Yonggang Wang
- Department of Cardiology, The First Hospital of Jilin University, Changchun, Jilin 130041, P.R. China
| | - Jing Sun
- Department of Nephrology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China
| | - Manyu Luo
- Department of Nephrology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China
| | - Wen Li
- Department of Nephrology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China
| | - Lining Miao
- Department of Nephrology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China
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Liu L, Sun X, Xie Y, Zhuang Y, Yao R, Xu K. Anti-Proliferative Activity of HPOB against Multiple Myeloma Cells via p21 Transcriptional Activation. Molecules 2018; 23:molecules23051044. [PMID: 29710846 PMCID: PMC6100322 DOI: 10.3390/molecules23051044] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Revised: 04/25/2018] [Accepted: 04/27/2018] [Indexed: 01/01/2023] Open
Abstract
Histone acetylation or deacetylation is closely associated with the progression of multiple myeloma (MM). Currently, many histone deacetylase (HDAC) inhibitors have been approved for being used in clinical trials, but theirtherapeutic effectsarestill not ideal. As a novel HDAC inhibitor, hydroxamicacid-based small-moleculeN-hydroxy-4-(2-[(2-hydroxyethyl)(phenyl)amino]-2-oxoethyl)benzamide (HPOB)’s possible roles in MM have not been studied. In this present study, the effect of HPOB as a potential anti-tumor agent in preventingproliferation and inducing apoptosis of MM cells had been investigated in detail. Our results showed that HPOB decreased the survival of MM cells in dose- and time-dependent manner. In addition, HPOB caused the accumulation of MM cells in G1 phase compared with the dimethylsulfoxide (DMSO) control group. Interestingly, we found that HPOB could overcome bortezomib (BTZ) resistance inMM cells and combining HPOB with BTZ could further sensitize MM cells. Certainly, our data illuminated that HPOB-mediated cell death occurs via transcriptional activation of p21, which was associated with an elevated level of global histone 3 acetylation (H3Ac) modification. Therefore, HPOB could be a potential candidate for MM treatment and the combination of HPOB and bortezomibcould bea possible therapeutic strategy for relapsed and refractory MM.
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Affiliation(s)
- Linlin Liu
- College of Medical Imaging, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
| | - Xiaoyang Sun
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
| | - Yu Xie
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
| | - Yinping Zhuang
- College of Medical Imaging, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
| | - Ruosi Yao
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
| | - Kai Xu
- College of Medical Imaging, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
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Xu Y, Hu J, Zhang C, Liu Y. MicroRNA‑320 targets mitogen‑activated protein kinase 1 to inhibit cell proliferation and invasion in epithelial ovarian cancer. Mol Med Rep 2017; 16:8530-8536. [PMID: 28990044 DOI: 10.3892/mmr.2017.7664] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2016] [Accepted: 06/21/2017] [Indexed: 11/06/2022] Open
Abstract
Ovarian cancer is the second most frequently occurring cancer and the most fatal gynecological malignancy of all gynecological cancers worldwide. MicroRNAs (miR) have been reported to be downregulated or upregulated in a variety of human malignancies, and involved in the formation and progression of the majority of human cancers, including epithelial ovarian cancer (EOC). miR‑320 has been identified as a tumor suppressor in multiple human cancers. However, the expression levels, biological role and underlying mechanisms of miR‑320 in EOC remain to be elucidated. In the present study, reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was performed to detect miR‑320 expression in EOC tissues and cell lines. Following transfection with miR‑320 mimics, Cell Counting Kit 8 and cell invasion assays were utilized to investigate the effects of miR‑320 on EOC cell proliferation and invasion. Bioinformatic analysis, luciferase reporter assay, RT‑qPCR and western blotting were used to explore the underlying mechanism of how miR‑320 affects cell proliferation and invasion in EOC. Mitogen‑activated protein kinase (MAPK) 1 expression and its association with the miR‑320 expression level was examined in EOC tissues. The role of MAPK1 in EOC cells was additionally evaluated by using a loss‑of‑function assay. The results demonstrated that miR‑320 was markedly downregulated in EOC tissues and cell lines. A decreased miR‑320 expression was significantly correlated with the Federation of Gynecology and Obstetrics stage and lymph node metastasis of EOC patients. Additionally, reintroduction of miR‑320 expression suppressed cell proliferation and invasion in EOC. Furthermore, it was verified that MAPK1 is a direct target gene of miR‑320 in EOC. MAPK1 expression was markedly upregulated in EOC tissues and inversely correlated with miR‑320 expression. Furthermore, silencing of MAPK1 by RNA interference inhibited cell proliferation and invasion of EOC cells. Overall, the present study demonstrated that miR‑320 may act as a useful diagnostic and therapeutic target in the treatment of EOC.
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Affiliation(s)
- Yongqian Xu
- Department of Gynecology and Obstetrics, Shengli Oilfield Central Hospital, Dongying, Shandong 257034, P.R. China
| | - Jian Hu
- Department of Gynecology and Obstetrics, Shengli Oilfield Central Hospital, Dongying, Shandong 257034, P.R. China
| | - Chunxia Zhang
- Department of Gynecology and Obstetrics, Shengli Oilfield Central Hospital, Dongying, Shandong 257034, P.R. China
| | - Yuanyuan Liu
- Department of Gynecology and Obstetrics, Shengli Oilfield Central Hospital, Dongying, Shandong 257034, P.R. China
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RNAi-mediated TCF-3 gene silencing inhibits proliferation of Eca-109 esophageal cancer cells by inducing apoptosis. Biosci Rep 2017; 37:BSR20170799. [PMID: 28864779 PMCID: PMC5678029 DOI: 10.1042/bsr20170799] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2017] [Revised: 08/24/2017] [Accepted: 08/30/2017] [Indexed: 01/24/2023] Open
Abstract
Esophageal cancer (EC) remains an important health problem in China. In the present study, through the use of siRNA, specific gene knockdown of transcription factor 3 gene (TCF-3) was achieved in vitro and the effect of TCF-3 gene on human EC Eca-109 cell proliferation and apoptosis. Eca-109 cells were treated using negative control (NC) of siRNA against TCF-3 (siTCF-3) and siTCF-3 group. Colony formation assay was used to detect the colony formation ability in Eca-109 cells. MTT assay was used to measure the cell growth and viability, whereas BrDU assay was used to evaluate cell proliferation, and flow cytometry (FCM) to assess cell apoptosis. Reverse-transcription quantitative PCR (RT-qPCR) was applied to measure TCF-3 gene expression. Protein expressions of TCF-3, apoptosis-related proteins, Bcl-2, Bax, and caspase-3 were determined using Western blotting. Transfection of siTCF-3 successfully down-regulated TCF-3 gene expression. In addition, siTCF-3, reduced Eca-109 cell viability and proliferation, in a time-dependent manner, and inhibited progression of cell cycle from G0/G1 to S-stage. When treated with siTCF-3, the Eca-109 cells exhibited increased apoptosis, with up-regulated cleaved caspase and Bax expressions, whereas Bcl-2 expression was down-regulated. The present study shows that TCF-3 gene silencing inhibits Eca-109 cell growth and proliferation, suppresses cell cycle progression, and promotes apoptosis, which might serve as a new objective for EC treatment.
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Zhang J, Guo F, Wei J, Xian M, Tang S, Zhao Y, Liu M, Song L, Geng Y, Yang H, Ding C, Huang L. An integrated approach to identify critical transcription factors in the protection against hydrogen peroxide-induced oxidative stress by Danhong injection. Free Radic Biol Med 2017; 112:480-493. [PMID: 28822748 DOI: 10.1016/j.freeradbiomed.2017.07.002] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2017] [Revised: 06/07/2017] [Accepted: 07/04/2017] [Indexed: 12/18/2022]
Abstract
Oxidative stress plays a vital role in many pathological processes of the cardiovascular diseases. However, the underlying mechanism remains unclear, especially on a transcription factor (TF) level. In this study, a new method, concatenated tandem array of consensus transcription factor response elements (catTFREs), and an Illumina-based RNA-seq technology were integrated to systematically investigate the role of TFs in hydrogen peroxide (H2O2)-induced oxidative stress in cardiomyocytes; the damage was then rescued by Danhong injection (DHI), a Chinese standardized product approved for cardiovascular diseases treatment. The overall gene expression revealed cell apoptosis and DNA repair were vital for cardiomyocytes in resisting oxidative stress. By comprehensively integrating the transcription activity of TFs and their downstream target genes, an important TFs-target network were constructed and 13 TFs were identified as critical TFs in DHI-mediated protection in H2O2-induced oxidative stress. By using the integrated approach, seven TFs of these 13 TFs were also identified in melatonin-mediated protection in H2O2-induced damage. Furthermore, the transcription activity of DNA-(apurinic or apyrimidinic site) lyase (Apex1), Myocyte-specific enhancer factor 2D (Mef2d) and Pre B-cell leukemia transcription factor 3 (Pbx3) was further verified in pluripotent stem cell-derived cardiomyocytes. This research offers a new understanding of cardiomyocytes in response to H2O2-induced oxidative stress and reveals additional potential therapeutic targets. The combination of two parallel omics datasets (corresponding to the transcriptome and proteome) can reduce the noise in high-throughput data and reveal the fundamental changes of the biological process, making it suitable and reliable for investigation of critical targets in many other complicated pathological processes.
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Affiliation(s)
- Jingjing Zhang
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Feifei Guo
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Junying Wei
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Minghua Xian
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Shihuan Tang
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Ye Zhao
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Mingwei Liu
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China
| | - Lei Song
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China
| | - Ya Geng
- School of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Hongjun Yang
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
| | - Chen Ding
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China; State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Fudan University, Shanghai 200433, China.
| | - Luqi Huang
- State Key Laboratory Breeding Base of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
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Xu X, Bao Z, Liu Y, Ji J, Liu N. MicroRNA-98 Attenuates Cell Migration and Invasion in Glioma by Directly Targeting Pre-B Cell Leukemia Homeobox 3. Cell Mol Neurobiol 2017; 37:1359-1371. [PMID: 28124208 PMCID: PMC11482209 DOI: 10.1007/s10571-017-0466-4] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2016] [Accepted: 01/18/2017] [Indexed: 01/07/2023]
Abstract
Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. The extraordinary invasion of human GBM into adjacent normal brain tissues contributes to treatment failure. However, the mechanisms that control this process remain poorly understood. Increasing evidence has demonstrated that microRNAs are strongly implicated in the migration and invasion of GBM. In this study, we found that microRNA-98 (miR-98) was markedly downregulated in human glioma tissues and cell lines. Functional experiments indicated that restored expression of miR-98 attenuated glioma cell invasion and migration, whereas depletion of miR-98 promoted glioma cell invasion and migration. Subsequent investigation showed that pre-B-cell leukemia homeobox 3 (PBX3), an important transcription factor that controls tumor invasion, was a direct and functional target of miR-98 in GBM cells. Consistently, an orthotopic mouse model also demonstrated the suppressive effects of miR-98 overexpression on tumor invasion and PBX3 expression. Silencing of PBX3 using small interfering RNA inhibited the migratory and invasive capacities of glioma cells, whereas reintroduction of PBX3 into glioma cells reversed the anti-invasive function of miR-98. Furthermore, depletion of PBX3 phenocopied the effects of miR-98 overexpression in vivo. Finally, quantitative real-time polymerase chain reaction results showed that miR-98 was negatively correlated with PBX3 expression in 24 glioma tissues. Thus, we propose that PBX3 modulation by miR-98 has an important role in regulating GBM invasion and may serve as therapeutic target for GBM.
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Affiliation(s)
- Xiupeng Xu
- Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Zhongyuan Bao
- Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Yinlong Liu
- Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Jing Ji
- Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
| | - Ning Liu
- Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
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Zhang J, Geng Y, Guo F, Zhang F, Liu M, Song L, Ma Y, Li D, Zhang Y, Xu H, Yang H. Screening and identification of critical transcription factors involved in the protection of cardiomyocytes against hydrogen peroxide-induced damage by Yixin-shu. Sci Rep 2017; 7:13867. [PMID: 29066842 PMCID: PMC5655617 DOI: 10.1038/s41598-017-10131-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2017] [Accepted: 08/04/2017] [Indexed: 01/12/2023] Open
Abstract
Oxidative stress initiates harmful cellular responses, such as DNA damage and protein denaturation, triggering a series of cardiovascular disorders. Systematic investigations of the transcription factors (TFs) involved in oxidative stress can help reveal the underlying molecular mechanisms and facilitate the discovery of effective therapeutic targets in related diseases. In this study, an integrated strategy which integrated RNA-seq-based transcriptomics techniques and a newly developed concatenated tandem array of consensus TF response elements (catTFREs)-based proteomics approach and then combined with a network pharmacology analysis, was developed and this integrated strategy was used to investigate critical TFs in the protection of Yixin-shu (YXS), a standardized medical product used for ischaemic heart disease, against hydrogen peroxide (H2O2)-induced damage in cardiomyocytes. Importantly, YXS initiated biological process such as anti-apoptosis and DNA repair to protect cardiomyocytes from H2O2-induced damage. By using the integrated strategy, DNA-(apurinic or apyrimidinic site) lyase (Apex1), pre B-cell leukemia transcription factor 3 (Pbx3), and five other TFs with their functions involved in anti-oxidation, anti-apoptosis and DNA repair were identified. This study offers a new understanding of the mechanism underlying YXS-mediated protection against H2O2-induced oxidative stress in cardiomyocytes and reveals novel targets for oxidative stress-related diseases.
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Affiliation(s)
- Jingjing Zhang
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Ya Geng
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
| | - Feifei Guo
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Fangbo Zhang
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Mingwei Liu
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, 102206, China
| | - Lei Song
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, 102206, China
| | - Yuexiang Ma
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
| | - Defeng Li
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Yi Zhang
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Haiyu Xu
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
| | - Hongjun Yang
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
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Liang L, Zeng JH, Wang JY, He RQ, Ma J, Chen G, Cai XY, Hu XH. Down-regulation of miR-26a-5p in hepatocellular carcinoma: A qRT-PCR and bioinformatics study. Pathol Res Pract 2017; 213:1494-1509. [PMID: 29113686 DOI: 10.1016/j.prp.2017.10.001] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2017] [Revised: 09/22/2017] [Accepted: 10/03/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND To practically verify the clinical value of miR-26a-5p and thoroughly explore its target genes as well as its potential functions in hepatocellular carcinoma (HCC). METHODS HCC and adjacent non-cancerous hepatic tissues of 95 HCC patients were collected for analysis using reverse transcription quantitative real-time PCR (qRT-PCR). For the bioinformatics analysis, we identified potential target genes for miR-26a-5p from differentially expressed genes (DEGs) in Gene Expression Omnibus (GEO) data sets and miRWalk predicted database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interaction (PPI) analyses were applied to analyze the prospective mechanisms of the predicted target genes. RESULTS MiR-26a-5p showed a significantly lower expression level in HCC tissues (1.56±1.07) than adjacent benign liver tissues (2.28±1.06, P<0.001). The area under the curve (AUC) of the receiver operating characteristic (ROC) was 0.665 (95% CI: 0.588-0.743, P<0.001). Significant correlations between miR-26a-5p expression and clinicopathological features such as gender (r=0.275, P<0.01), clinical TNM stage (r=-0.306, P<0.01), and metastasis (r=-0.321, P<0.01) were observed. To examine potential target genes, we obtained 175 genes for further function analysis, by attaining the intersection of 2062 up-regulated DEGs and 1390 online-predicted target genes. The GO and KEGG pathway annotation indicated focal adhesion, regulation of actin cytoskeleton and the PI3K-Akt signaling pathway as significant prospective mechanisms. The PPI network indicated that NRAS was the most essential hub gene in the whole network. CONCLUSION Down-regulated miR-26a-5p was closely correlated with the status of metastasis and the progression of HCC. MiR-26a-5p might play protective roles by targeting diverse genes and pathways.
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Affiliation(s)
- Liang Liang
- Department of General Surgery, Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, PR China
| | - Jiang-Hui Zeng
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, PR China
| | - Jie-Yu Wang
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, PR China
| | - Rong-Quan He
- Department of Medical Oncology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, PR China
| | - Jie Ma
- Department of Medical Oncology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, PR China
| | - Gang Chen
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, PR China
| | - Xiao-Yong Cai
- Department of General Surgery, Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, PR China.
| | - Xiao-Hua Hu
- Department of Medical Oncology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, PR China.
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Xu X, Cai N, Bao Z, You Y, Ji J, Liu N. Silencing Pre-B-cell leukemia homeobox 3 decreases the proliferation of human glioma cells in vitro and in vivo. J Neurooncol 2017; 135:453-463. [PMID: 28856521 DOI: 10.1007/s11060-017-2603-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2016] [Accepted: 08/20/2017] [Indexed: 01/28/2023]
Abstract
Among primary brain tumors, gliomas are the most common and most aggressive, with a poor prognosis and limited treatment options. Thus, it is essential to determine the mechanisms involved in glioma development to develop effective therapies for glioma patients. Pre-B-cell leukemia homeobox 3 (PBX3), a critical member of the PBX family, is frequently overexpressed in multiple human malignancies. However, the expression patterns and biological functions, as well as the involved molecular functions of PBX3 in human gliomas remain largely unknown. In this study, we demonstrate that PBX3 expression is increased in both human glioma tissues and cell lines compared with their normal counterparts. These results suggested that PBX3 might be involved in glioma progression. Thus, the role of PBX3 in glioma cell proliferation was investigated using genetic knockdown and overexpression methods. The results showed that PBX3 knockdown inhibited glioma cell proliferation and induced apoptosis, while PBX3 overexpression significantly promoted glioma cell proliferation. Mechanistically, we found that PBX3 promoted cell proliferation by modulating cell cycle progression. A xenograft LN229 model was used to confirm that PBX3 depletion decreased tumor growth in vivo. In summary, our findings reveal that PBX3 may be a potential therapeutic target in gliomas.
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Affiliation(s)
- Xiupeng Xu
- Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 222000, Jiangsu, China
| | - Ning Cai
- Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 222000, Jiangsu, China
| | - Zhongyuan Bao
- Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 222000, Jiangsu, China
| | - Yongping You
- Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 222000, Jiangsu, China
| | - Jing Ji
- Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 222000, Jiangsu, China
| | - Ning Liu
- Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 222000, Jiangsu, China.
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Yang N, Chen J, Zhang H, Wang X, Yao H, Peng Y, Zhang W. LncRNA OIP5-AS1 loss-induced microRNA-410 accumulation regulates cell proliferation and apoptosis by targeting KLF10 via activating PTEN/PI3K/AKT pathway in multiple myeloma. Cell Death Dis 2017; 8:e2975. [PMID: 28796257 PMCID: PMC5596549 DOI: 10.1038/cddis.2017.358] [Citation(s) in RCA: 135] [Impact Index Per Article: 16.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2017] [Revised: 06/15/2017] [Accepted: 06/23/2017] [Indexed: 12/16/2022]
Abstract
Numerous studies confirmed that aberrant miRNAs expression contributes to multiple myeloma (MM) development and progression. However, the roles of specific miRNAs in MM remain to be investigated. In present study, we demonstrated that miR-410 expression was increased in MM newly diagnosed and relapsed tissues and cell lines. Clinical analysis revealed that miR-410 was positively correlated with advanced ISS stage. Moreover, high miR-410 expression in MM patients showed an obvious shorter overall survival and progression-free survival. Gain- and loss-of function experiments indicated that miR-410 promoted cell proliferation, cell cycle progression and apoptosis inhibition both in vitro and in vivo. Moreover, KLF10 was identified as a direct downstream target of miR-410 in MM cells, and mediated the functional influence of miR-410 in MM, resulting in PTEN/AKT activation. In clinical samples of MM, miR-410 inversely correlated with KLF10. Alteration of KLF10 expression or AKT inhibitor at least partially abolished the biological effects of miR-410 on MM cells. Furthermore, downregulated expression of lncRNA OIP5-AS1 was inversely correlated with miR-410 expression in MM tissues. LncRNA OIP5-AS1 could modulate the miR-410 expression and regulate its target KLF10/PTEN/AKT-mediated cellular behaviors. Taken together, this research supports the first evidence that lncRNA OIP5-AS1 loss-induced miR-410 accumulation facilitates cell proliferation, cycle progression and apoptosis inhibition by targeting KLF10 via activating PTEN/PI3K/AKT pathway in MM.
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Affiliation(s)
- Nan Yang
- Department of Hematology, The Second Affiliated Hospital of Xi’an Jiaotong University, West Five Road, NO.157, Xi’an, China
| | - Jinqiu Chen
- Department of Hematology, The Second Affiliated Hospital of Xi’an Jiaotong University, West Five Road, NO.157, Xi’an, China
| | - Hui Zhang
- Department of Hematology, The Second Affiliated Hospital of Xi’an Jiaotong University, West Five Road, NO.157, Xi’an, China
| | - Xiaman Wang
- Department of Hematology, The Second Affiliated Hospital of Xi’an Jiaotong University, West Five Road, NO.157, Xi’an, China
| | - Huan Yao
- Department of Hematology, The Second Affiliated Hospital of Xi’an Jiaotong University, West Five Road, NO.157, Xi’an, China
| | - Yue Peng
- Department of Hematology, The Second Affiliated Hospital of Xi’an Jiaotong University, West Five Road, NO.157, Xi’an, China
| | - Wanggang Zhang
- Department of Hematology, The Second Affiliated Hospital of Xi’an Jiaotong University, West Five Road, NO.157, Xi’an, China
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Meinzinger J, Jäck HM, Pracht K. miRNA meets plasma cells "How tiny RNAs control antibody responses". Clin Immunol 2017; 186:3-8. [PMID: 28736279 DOI: 10.1016/j.clim.2017.07.015] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Accepted: 07/19/2017] [Indexed: 01/10/2023]
Abstract
We review the importance of small non-coding microRNAs for the generation of germinal center B cells and their differentiation in antibody-secreting plasma cells. In the last part, we briefly elucidate the role of microRNAs in some plasma cell disorders.
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Affiliation(s)
- Julia Meinzinger
- Division of Molecular Immunology, Internal Medicine III, Nikolaus-Fiebiger-Center of MolecularMedicine, University Hospital Erlangen, Erlangen, Germany
| | - Hans-Martin Jäck
- Division of Molecular Immunology, Internal Medicine III, Nikolaus-Fiebiger-Center of MolecularMedicine, University Hospital Erlangen, Erlangen, Germany.
| | - Katharina Pracht
- Division of Molecular Immunology, Internal Medicine III, Nikolaus-Fiebiger-Center of MolecularMedicine, University Hospital Erlangen, Erlangen, Germany
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Abstract
Objectives This study aimed to explore the role of miR-320a in the pathogenesis of osteoarthritis (OA). Methods Human cartilage cells (C28/I2) were transfected with miR-320a or antisense oligonucleotides (ASO)-miR-320a, and treated with IL-1β. Subsequently the expression of collagen type II alpha 1 (Col2α1) and aggrecan (ACAN), and the concentrations of sulfated glycosaminoglycans (sGAG) and matrix metallopeptidase 13 (MMP-13), were assessed. Luciferase reporter assay, qRT-PCR, and Western blot were performed to explore whether pre-B-cell leukemia Homeobox 3 (PBX3) was a target of miR-320a. Furthermore, cells were co-transfected with miR-320a and PBX3 expressing vector, or cells were transfected with miR-320a and treated with a nuclear factor kappa B (NF-κB) antagonist MG132. The changes in Col2α1 and ACAN expression, and in sGAG and MMP-13 concentrations, were measured again. Statistical comparisons were made between two groups by using the two-tailed paired t-test. Results Expression of miR-320a was elevated in OA cartilage tissues and chondrocytes, and in IL-1β-stimulated C28/I2 cells (p < 0.05 or p < 0.01). MiR-320a overexpression enhanced IL-1β-induced down-regulation of Col2α1 and ACAN and sGAG, and increased the IL-1β-induced overexpression of MMP-13 (p < 0.01). PBX3 was a direct target of miR-320a. PBX3 and MG132 co-transfection attenuated the effects of miR-320a on the expression of Col2α1, ACAN, sGAG and MMP-13(p < 0.01). Conclusion Overexpression of miR-320a might enhance IL-1β-induced cartilage degradation factors. These effects might be via targeting PBX3 and regulating NF-κB. Cite this article: Y. Jin, X. Chen, Z. Y. Gao, K. Liu, Y. Hou, J. Zheng. The role of miR-320a and IL-1β in human chondrocyte degradation. Bone Joint Res 2017;6:–203. DOI: 10.1302/2046-3758.64.BJR-2016-0224.R1.
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Affiliation(s)
- Y Jin
- Department of Orthopaedics, Henan Provincial People's Hospital (Zhengzhou University People's Hospital), Zhengzhou 450003, China
| | - X Chen
- Department of Orthopaedics, Henan Provincial People's Hospital (Zhengzhou University People's Hospital), Zhengzhou 450003, China
| | - Z Y Gao
- Department of Orthopaedics, Henan Provincial People's Hospital (Zhengzhou University People's Hospital), Zhengzhou 450003, China
| | - K Liu
- Department of Orthopaedics, Henan Provincial People's Hospital (Zhengzhou University People's Hospital), Zhengzhou 450003, China
| | - Y Hou
- Department of Orthopaedics, Henan Provincial People's Hospital (Zhengzhou University People's Hospital), Zhengzhou 450003, China
| | - J Zheng
- Department of Orthopaedics, Henan Provincial People's Hospital (Zhengzhou University People's Hospital), Zhengzhou 450003, China
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Xiang T, Hu AX, Sun P, Liu G, Liu G, Xiao Y. Identification of four potential predicting miRNA biomarkers for multiple myeloma from published datasets. PeerJ 2017; 5:e2831. [PMID: 28168095 PMCID: PMC5289111 DOI: 10.7717/peerj.2831] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2016] [Accepted: 11/24/2016] [Indexed: 12/19/2022] Open
Abstract
Background Multiple myeloma is a cancer which has a high occurrence rate and causes great injury to people worldwide. In recent years, many studies reported the effects of miRNA on the appearance of multiple myeloma. However, due to the differences of samples and sequencing platforms, a large number of inconsistent results have been generated among these studies, which limited the cure of multiple myeloma at the miRNA level. Methods We performed meta-analyses to identify the key miRNA biomarkers which could be applied on the treatment of multiple myeloma. The key miRNAs were determined by overlap comparisons of seven datasets in multiple myeloma. Then, the target genes for key miRNAs were predicted by the software TargetScan. Additionally, functional enrichments and binding TFs were investigated by DAVID database and Tfacts database, respectively. Results Firstly, comparing the normal tissues, 13 miRNAs were differently expressed miRNAs (DEMs) for at least three datasets. They were considered as key miRNAs, with 12 up-regulated (hsa-miR-106b, hsa-miR-125b, hsa-miR-130b, hsa-miR-138, hsa-miR-15b, hsa-miR-181a, hsa-miR-183, hsa-miR-191, hsa-miR-19a, hsa-miR-20a, hsa-miR-221 and hsa-miR-25) and one down-regulated (hsa-miR-223). Secondly, functional enrichment analyses indicated that target genes of the upregulated miRNAs were mainly transcript factors and enriched in transcription regulation. Besides, these genes were enriched in multiple pathways: the cancer signal pathway, insulin signal metabolic pathway, cell binding molecules, melanin generation, long-term regression and P53 signaling pathway. However, no significant enrichment was found for target genes of the down-regulated genes. Due to the distinct regulation function, four miRNAs (hsa-miR-19a has-miR-221 has-miR25 and has-miR223) were ascertained as the potential prognostic and diagnostic markers in MM. Thirdly, transcript factors analysis unveiled that there were 148 TFs and 60 TFs which bind target genes of the up-regulated miRNAs and target genes of the down-regulated miRNAs, respectively. They respectively generated 652 and 139 reactions of TFs and target genes. Additionally, 50 (31.6%) TFs were shared, while higher specificity was found in TFs of target genes for the upregulated miRNAs. Discussions Together, our findings provided the key miRNAs which affected occurrence of multiple myeloma and regulation function of these miRNAs. It is valuable for the prognosis and diagnosis of multiple myeloma.
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Affiliation(s)
- Tian Xiang
- Department of Clinical Laboratory Center, Central Hospital of Enshi Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, Hubei, China
| | - Ai-Xin Hu
- The Department of Orthopedic Surgery, People's Hospital of Three Gorges University, YiChang, Hubei, China
| | - Peng Sun
- Department of Orthopedics, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, China
| | - Gao Liu
- Department of Gastrointestinal Surgery, Central Hospital of Enshi Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, Hubei, China
| | - Gang Liu
- Department of Orthopedics, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, China
| | - Yan Xiao
- Department of Hematology, The Affiliated Huai'an Hospital of Xuzhou Medical College and The Second People's Hospital of Huai'an, Huai'an, China
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Chang JTH, Wang F, Chapin W, Huang RS. Identification of MicroRNAs as Breast Cancer Prognosis Markers through the Cancer Genome Atlas. PLoS One 2016; 11:e0168284. [PMID: 27959953 PMCID: PMC5154569 DOI: 10.1371/journal.pone.0168284] [Citation(s) in RCA: 75] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Accepted: 11/29/2016] [Indexed: 12/21/2022] Open
Abstract
Breast cancer is the second-most common cancer and second-leading cause of cancer mortality in American women. The dysregulation of microRNAs (miRNAs) plays a key role in almost all cancers, including breast cancer. We comprehensively analyzed miRNA expression, global gene expression, and patient survival from the Cancer Genomes Atlas (TCGA) to identify clinically relevant miRNAs and their potential gene targets in breast tumors. In our analysis, we found that increased expression of 12 mature miRNAs-hsa-miR-320a, hsa-miR-361-5p, hsa-miR-103a-3p, hsa-miR-21-5p, hsa-miR-374b-5p, hsa-miR-140-3p, hsa-miR-25-3p, hsa-miR-651-5p, hsa-miR-200c-3p, hsa-miR-30a-5p, hsa-miR-30c-5p, and hsa-let-7i-5p -each predicted improved breast cancer survival. Of the 12 miRNAs, miR-320a, miR-361-5p, miR-21-5p, miR-103a-3p were selected for further analysis. By correlating global gene expression with miRNA expression and then employing miRNA target prediction analysis, we suggest that the four miRNAs may exert protective phenotypes by targeting breast oncogenes that contribute to patient survival. We propose that miR-320a targets the survival-associated genes RAD51, RRP1B, and TDG; miR-361-5p targets ARCN1; and miR-21-5p targets MSH2, RMND5A, STAG2, and UBE2D3. The results of our stringent bioinformatics approach for identifying clinically relevant miRNAs and their targets indicate that miR-320a, miR-361-5p, and miR-21-5p may contribute to breast cancer survival.
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Affiliation(s)
- Jeremy T-H. Chang
- Biological Sciences Collegiate Division, University of Chicago, Chicago, Illinois, United States of America
| | - Fan Wang
- Department of Medicine, University of Chicago, Chicago, Illinois, United States of America
| | - William Chapin
- Pritzker School of Medicine, University of Chicago, Chicago, Illinois, United States of America
| | - R. Stephanie Huang
- Department of Medicine, University of Chicago, Chicago, Illinois, United States of America
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Xu Z, Huang C, Hao D. MicroRNA-1271 inhibits proliferation and promotes apoptosis of multiple myeloma cells through inhibiting smoothened-mediated Hedgehog signaling pathway. Oncol Rep 2016; 37:1261-1269. [DOI: 10.3892/or.2016.5304] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2016] [Accepted: 11/16/2016] [Indexed: 11/05/2022] Open
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