|
1
|
Borg J, Loy C, Kim J, Buhagiar A, Chin C, Damle N, De Vlaminck I, Felice A, Liu T, Matei I, Meydan C, Muratani M, Mzava O, Overbey E, Ryon KA, Smith SM, Tierney BT, Trudel G, Zwart SR, Beheshti A, Mason CE, Borg J. Spatiotemporal expression and control of haemoglobin in space. Nat Commun 2024; 15:4927. [PMID: 38862545 PMCID: PMC11166948 DOI: 10.1038/s41467-024-49289-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Accepted: 05/31/2024] [Indexed: 06/13/2024] Open
Abstract
It is now widely recognised that the environment in space activates a diverse set of genes involved in regulating fundamental cellular pathways. This includes the activation of genes associated with blood homoeostasis and erythropoiesis, with a particular emphasis on those involved in globin chain production. Haemoglobin biology provides an intriguing model for studying space omics, as it has been extensively explored at multiple -omic levels, spanning DNA, RNA, and protein analyses, in both experimental and clinical contexts. In this study, we examined the developmental expression of haemoglobin over time and space using a unique suite of multi-omic datasets available on NASA GeneLab, from the NASA Twins Study, the JAXA CFE study, and the Inspiration4 mission. Our findings reveal significant variations in globin gene expression corresponding to the distinct spatiotemporal characteristics of the collected samples. This study sheds light on the dynamic nature of globin gene regulation in response to the space environment and provides valuable insights into the broader implications of space omics research.
Collapse
Affiliation(s)
- Josef Borg
- Faculty of Health Sciences, University of Malta, Msida, MSD2080, Malta
| | - Conor Loy
- Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA
| | - JangKeun Kim
- Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA
| | - Alfred Buhagiar
- Faculty of Health Sciences, University of Malta, Msida, MSD2080, Malta
| | - Christopher Chin
- Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA
| | - Namita Damle
- Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA
| | - Iwijn De Vlaminck
- Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA
| | - Alex Felice
- Department of Surgery, Faculty of Medicine and Surgery, University of Malta, Msida, MSD2080, Malta
| | - Tammy Liu
- Ottawa Hospital Research Institute, Department of Medicine, Ottawa, Ontario, Canada
| | - Irina Matei
- Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA
| | - Cem Meydan
- Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA
| | - Masafumi Muratani
- Department of Genome Biology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Omary Mzava
- Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA
| | - Eliah Overbey
- Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA
| | - Krista A Ryon
- Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA
| | - Scott M Smith
- Biomedical Research and Environmental Sciences Division, Human Health and Performance Directorate, NASA Johnson Space Center, Houston, TX, USA
| | - Braden T Tierney
- Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA
| | - Guy Trudel
- Ottawa Hospital Research Institute, Department of Medicine, Ottawa, Ontario, Canada
| | - Sara R Zwart
- Biomedical Research and Environmental Sciences Division, Human Health and Performance Directorate, NASA Johnson Space Center, Houston, TX, USA
- University of Texas Medical Branch, Galveston, TX, USA
| | - Afshin Beheshti
- Blue Marble Space Institute of Science, Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA, USA.
- Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
| | - Christopher E Mason
- Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.
- The WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine, New York, NY, 10065, USA.
| | - Joseph Borg
- Faculty of Health Sciences, University of Malta, Msida, MSD2080, Malta.
| |
Collapse
|
|
2
|
Ma Y, Shi Y, Chen X, Zhang B, Wu H, Gao J. NFMCLDA: Predicting miRNA-based lncRNA-disease associations by network fusion and matrix completion. Comput Biol Med 2024; 174:108403. [PMID: 38582002 DOI: 10.1016/j.compbiomed.2024.108403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 03/28/2024] [Accepted: 04/01/2024] [Indexed: 04/08/2024]
Abstract
In recent years, emerging evidence has revealed a strong association between dysregulations of long non-coding RNAs (lncRNAs) and sophisticated human diseases. Biological experiments are adequate to identify such associations, but they are costly and time-consuming. Therefore, developing high-quality computational methods is a challenging and urgent task in the field of bioinformatics. This paper proposes a new lncRNA-disease association inference approach NFMCLDA (Network Fusion and Matrix Completion lncRNA-Disease Association), which can effectively integrate multi-source association data. In this approach, miRNA information is used as the transition path, and an unbalanced random walk method on three-layer heterogeneous network is adopted in the preprocessing. Therefore, more effective information between networks can be mined and the sparsity problem of the association matrix can be solved. Finally, the matrix completion method accurately predicts associations. The results show that NFMCLDA can provide more accurate lncRNA-disease associations than state-of-the-art methods. The areas under the receiver operating characteristic curves are 0.9648 and 0.9713, respectively, through the cross-validation of 5-fold and 10-fold. Data from published case studies on four diseases - lung cancer, osteosarcoma, cervical cancer, and colon cancer - have confirmed the reliable predictive potential of NFMCLDA model.
Collapse
Affiliation(s)
- Yibing Ma
- School of Science, Jiangnan University, Wuxi, Jiangsu, 214122, China
| | - Yongle Shi
- School of Science, Jiangnan University, Wuxi, Jiangsu, 214122, China
| | - Xiang Chen
- School of Science, Jiangnan University, Wuxi, Jiangsu, 214122, China
| | - Bai Zhang
- School of Science, Jiangnan University, Wuxi, Jiangsu, 214122, China
| | - Hanwen Wu
- School of Science, Jiangnan University, Wuxi, Jiangsu, 214122, China
| | - Jie Gao
- School of Science, Jiangnan University, Wuxi, Jiangsu, 214122, China.
| |
Collapse
|
|
3
|
Tao ZG, Yuan YX, Wang GW. Long non-coding RNA CDKN2B-AS1 promotes hepatocellular carcinoma progression via E2F transcription factor 1/G protein subunit alpha Z axis. World J Gastrointest Oncol 2023; 15:1974-1987. [DOI: 10.4251/wjgo.v15.i11.1974] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 09/12/2023] [Accepted: 10/11/2023] [Indexed: 11/15/2023] Open
Abstract
BACKGROUND A series of long non-coding RNAs (lncRNAs) have been reported to play a crucial role in cancer biology. Some previous studies report that lncRNA CDKN2B-AS1 is involved in some human malignancies. However, its role in hepatocellular carcinoma (HCC) has not been fully deciphered.
AIM To decipher the role of CDKN2B-AS1 in the progression of HCC.
METHODS CDKN2B-AS1 expression in HCC was detected by quantitative real-time polymerase chain reaction. The malignant phenotypes of Li-7 and SNU-182 cells were detected by the CCK-8 method, EdU method, and flow cytometry, respectively. RNA immunoprecipitation was executed to confirm the interaction between CDKN2B-AS1 and E2F transcription factor 1 (E2F1). Luciferase reporter assay and chromatin immunoprecipitation were performed to verify the binding of E2F1 to the promoter of G protein subunit alpha Z (GNAZ). E2F1 and GNAZ were detected by western blot in HCC cells.
RESULTS In HCC tissues, CDKN2B-AS1 was upregulated. Depletion of CDKN2B-AS1 inhibited the proliferation of HCC cells, and the depletion of CDKN2B-AS1 also induced cell cycle arrest and apoptosis. CDKN2B-AS1 could interact with E2F1. Depletion of CDKN2B-AS1 inhibited the binding of E2F1 to the GNAZ promoter region. Overexpression of E2F1 reversed the biological effects of depletion of CDKN2B-AS1 on the malignant behaviors of HCC cells.
CONCLUSION CDKN2B-AS1 recruits E2F1 to facilitate GNAZ transcription to promote HCC progression.
Collapse
Affiliation(s)
- Zhi-Gang Tao
- Department of Radiology, Hangzhou Cancer Hospital, Hangzhou 310000, Zhejiang Province, China
| | - Yu-Xiao Yuan
- Department of Radiology, Hangzhou Xixi Hospital, Hangzhou 310012, Zhejiang Province, China
| | - Guo-Wei Wang
- Department of Radiology, Hangzhou Xixi Hospital, Hangzhou 310012, Zhejiang Province, China
| |
Collapse
|
|
4
|
Sanchez A, Lhuillier J, Grosjean G, Ayadi L, Maenner S. The Long Non-Coding RNA ANRIL in Cancers. Cancers (Basel) 2023; 15:4160. [PMID: 37627188 PMCID: PMC10453084 DOI: 10.3390/cancers15164160] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 08/14/2023] [Accepted: 08/15/2023] [Indexed: 08/27/2023] Open
Abstract
ANRIL (Antisense Noncoding RNA in the INK4 Locus), a long non-coding RNA encoded in the human chromosome 9p21 region, is a critical factor for regulating gene expression by interacting with multiple proteins and miRNAs. It has been found to play important roles in various cellular processes, including cell cycle control and proliferation. Dysregulation of ANRIL has been associated with several diseases like cancers and cardiovascular diseases, for instance. Understanding the oncogenic role of ANRIL and its potential as a diagnostic and prognostic biomarker in cancer is crucial. This review provides insights into the regulatory mechanisms and oncogenic significance of the 9p21 locus and ANRIL in cancer.
Collapse
Affiliation(s)
| | | | | | - Lilia Ayadi
- CNRS, Université de Lorraine, IMoPA, F-54000 Nancy, France
| | | |
Collapse
|
|
5
|
Dai J, Qu T, Yin D, Cui Y, Zhang C, Zhang E, Guo R. LncRNA LINC00969 promotes acquired gefitinib resistance by epigenetically suppressing of NLRP3 at transcriptional and posttranscriptional levels to inhibit pyroptosis in lung cancer. Cell Death Dis 2023; 14:312. [PMID: 37156816 PMCID: PMC10167249 DOI: 10.1038/s41419-023-05840-x] [Citation(s) in RCA: 54] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Revised: 04/26/2023] [Accepted: 04/28/2023] [Indexed: 05/10/2023]
Abstract
Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment prolongs the survival of lung cancer patients harbouring activating EGFR mutations. However, resistance to EGFR-TKIs is inevitable after long-term treatment. Molecular mechanistic research is of great importance in combatting resistance. A comprehensive investigation of the molecular mechanisms underlying resistance has important implications for overcoming resistance. An accumulating body of evidence shows that lncRNAs can contribute to tumorigenesis and treatment resistance. By bioinformatics analysis, we found that LINC00969 expression was elevated in lung cancer cells with acquired gefitinib resistance. LINC00969 regulated resistance to gefitinib in vitro and in vivo. Mechanistically, gain of H3K4me1 and H3K27Ac led to the activation of LINC00969 expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NLRP3 promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner, thus epigenetically repressing NLRP3 expression to suppress the activation of the NLRP3/caspase-1/GSDMD-related classical pyroptosis signalling pathways, thereby endowing an antipyroptotic phenotype and promoting TKI resistance in lung cancer. Our findings provide a new mechanism for lncRNA-mediated TKI resistance from the new perspective of pyroptosis via simultaneous regulation of histone methylation and RNA methylation. The pivotal role of LINC00969 gives it the potential to be a novel biomarker and therapeutic target for overcoming EGFR-TKI resistance in lung cancer.
Collapse
Affiliation(s)
- Jiali Dai
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, P. R. China
| | - Tianyu Qu
- Department of Respiratory Medicine, Zhongda Hospital of Southeast University, Nanjing, Jiangsu, 210009, P. R. China
| | - Dandan Yin
- Clinical Research Center, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210003, P. R. China
| | - Yanan Cui
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, P. R. China
| | - Chen Zhang
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, P. R. China
| | - Erbao Zhang
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, P. R. China.
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, P. R. China.
| | - Renhua Guo
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, P. R. China.
| |
Collapse
|
|
6
|
Lin L, Chen R, Zhu Y, Xie W, Jing H, Chen L, Zou M. SCCPMD: Probability matrix decomposition method subject to corrected similarity constraints for inferring long non-coding RNA-disease associations. Front Microbiol 2023; 13:1093615. [PMID: 36713213 PMCID: PMC9874942 DOI: 10.3389/fmicb.2022.1093615] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 11/30/2022] [Indexed: 01/13/2023] Open
Abstract
Accumulating evidence has demonstrated various associations of long non-coding RNAs (lncRNAs) with human diseases, such as abnormal expression due to microbial influences that cause disease. Gaining a deeper understanding of lncRNA-disease associations is essential for disease diagnosis, treatment, and prevention. In recent years, many matrix decomposition methods have also been used to predict potential lncRNA-disease associations. However, these methods do not consider the use of microbe-disease association information to enrich disease similarity, and also do not make more use of similarity information in the decomposition process. To address these issues, we here propose a correction-based similarity-constrained probability matrix decomposition method (SCCPMD) to predict lncRNA-disease associations. The microbe-disease associations are first used to enrich the disease semantic similarity matrix, and then the logistic function is used to correct the lncRNA and disease similarity matrix, and then these two corrected similarity matrices are added to the probability matrix decomposition as constraints to finally predict the potential lncRNA-disease associations. The experimental results show that SCCPMD outperforms the five advanced comparison algorithms. In addition, SCCPMD demonstrated excellent prediction performance in a case study for breast cancer, lung cancer, and renal cell carcinoma, with prediction accuracy reaching 80, 100, and 100%, respectively. Therefore, SCCPMD shows excellent predictive performance in identifying unknown lncRNA-disease associations.
Collapse
Affiliation(s)
- Lieqing Lin
- Center of Campus Network & Modern Educational Technology, Guangdong University of Technology, Guangzhou, China
| | - Ruibin Chen
- School of Computer, Guangdong University of Technology, Guangzhou, China
| | - Yinting Zhu
- School of Computer, Guangdong University of Technology, Guangzhou, China
| | - Weijie Xie
- School of Computer, Guangdong University of Technology, Guangzhou, China
| | - Huaiguo Jing
- Sports Department, Guangdong University of Technology, Guangzhou, China
| | - Langcheng Chen
- Center of Campus Network & Modern Educational Technology, Guangdong University of Technology, Guangzhou, China
| | - Minqing Zou
- Department of Experiment Teaching, Guangdong University of Technology, Guangzhou, China
| |
Collapse
|
|
7
|
Chen Y, Wang W, Fang L, Zhang Z, Deng S. Identification of PTK2 as an adverse prognostic biomarker in breast cancer by integrated bioinformatics and experimental analyses. Front Mol Biosci 2022; 9:984564. [PMID: 36533074 PMCID: PMC9751198 DOI: 10.3389/fmolb.2022.984564] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Accepted: 11/14/2022] [Indexed: 08/09/2023] Open
Abstract
PTK2 is highly expressed in many cancers and is involved in cell growth, survival, migration, and invasion. However, the prognostic value of PTK2 and its potential function remain unclear in breast cancer. Therefore, we performed a comprehensive analysis of multiple public databases to explore the roles of PTK2. By integrating multiple datasets, we found that PTK2 mRNA expression in breast cancer tissue was higher than that in normal breast tissue or adjacent tissue. High PTK2 expression was associated with lymph node metastasis stage, tumor stage, breast cancer type, age, TP53 mutation, and gender and significantly predicted a poor survival outcome in breast cancer patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) results suggested that PTK2 and co-expressed genes participated in the cell cycle. Immune infiltration analysis clarified that high PTK2 expression was positively correlated with infiltrating levels of CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. The DNA methylation of PTK2 in breast cancer tissues was higher than that in normal tissues, and high PTK2 methylation was correlated with poor prognosis in breast cancer patients. Furthermore, 16 possible ceRNA networks related to PTK2 were constructed for breast cancer. Additionally, PTK2 knockdown could suppress the proliferation and migration ability of MCF-7 cells. These results suggest that PTK2 can be used as a prognostic biomarker for breast cancer.
Collapse
Affiliation(s)
- Yanru Chen
- North Sichuan Medical College, Institute of Basic Medicine and Forensic Medicine, Sichuan, China
- Sichuan Key Laboratory of Medical Imaging and school of Medicine Imaging, North Sichuan Medical College, Sichuan, China
- Department of Academician (expert) Workstation, Biological Targeting Laboratory of Breast Cancer, Breast and Thyroid Surgery, Affiliated Hospital of North Sichuan Medical College, Sichuan, China
| | - Wei Wang
- Wuxi School of Medicine, Jiangnan University, Jiangsu, China
| | - Lingyu Fang
- North Sichuan Medical College, Institute of Basic Medicine and Forensic Medicine, Sichuan, China
- Sichuan Key Laboratory of Medical Imaging and school of Medicine Imaging, North Sichuan Medical College, Sichuan, China
- Department of Academician (expert) Workstation, Biological Targeting Laboratory of Breast Cancer, Breast and Thyroid Surgery, Affiliated Hospital of North Sichuan Medical College, Sichuan, China
| | - Zhenyang Zhang
- North Sichuan Medical College, Institute of Basic Medicine and Forensic Medicine, Sichuan, China
- Sichuan Key Laboratory of Medical Imaging and school of Medicine Imaging, North Sichuan Medical College, Sichuan, China
- Department of Academician (expert) Workstation, Biological Targeting Laboratory of Breast Cancer, Breast and Thyroid Surgery, Affiliated Hospital of North Sichuan Medical College, Sichuan, China
| | - Shishan Deng
- North Sichuan Medical College, Institute of Basic Medicine and Forensic Medicine, Sichuan, China
- Sichuan Key Laboratory of Medical Imaging and school of Medicine Imaging, North Sichuan Medical College, Sichuan, China
- Department of Academician (expert) Workstation, Biological Targeting Laboratory of Breast Cancer, Breast and Thyroid Surgery, Affiliated Hospital of North Sichuan Medical College, Sichuan, China
| |
Collapse
|
|
8
|
Li H, Lin D, Yu Z, Li H, Zhao S, Hainisayimu T, Liu L, Wang K. A nomogram model based on the number of examined lymph nodes-related signature to predict prognosis and guide clinical therapy in gastric cancer. Front Immunol 2022; 13:947802. [PMID: 36405735 PMCID: PMC9667298 DOI: 10.3389/fimmu.2022.947802] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Accepted: 09/30/2022] [Indexed: 01/25/2023] Open
Abstract
BACKGROUND Increasing evidence suggests that the number of examined lymph nodes (ELNs) is strongly linked to the survivorship of gastric cancer (GC). The goal of this study was to assess the prognostic implications of the ELNs number and to construct an ELNs-based risk signature and nomogram model to predict overall survival (OS) characteristics in GC patients. METHODS This inception cohort study included 19,317 GC patients from the U.S. Surveillance, Epidemiology, and End Results (SEER) database, who were separated into a training group and an internal validation group. The nomogram was built with the training set, then internally verified with SEER data, and externally validated with two different data sets. Based on the RNA-seq data, ELNs-related DERNAs (DElncRNAs, DEmiRNAs, andDEmRNAs) and immune cells were identified. The LASSO-Cox regression analysis was utilized to construct ELNs-related DERNAs and immune cell prognostic signature in The Cancer Genome Atlas (TCGA) cohort. The OS of subgroups with high- and low-ELN signature was compared using the Kaplan-Meier (K-M) analysis. A nomogram was successfully constructed based on the ELNs signature and other clinical characteristics. The concordance index (C-index), calibration plot, receiver operating characteristic curve, and decision curve analysis (DCA) were all used to evaluate the nomogram model. The meta-analysis, the Gene Expression Profiling Interactive Analysis database, and reverse transcription-quantitative PCR (RT-qPCR) were utilized to validate the RNA expression or abundance of prognostic genes and immune cells between GC tissues and normal gastric tissues, respectively. Finally, we analyzed the correlations between immune checkpoints, chemotherapy drug sensitivity, and risk score. RESULTS The multivariate analysis revealed that the high ELNs improved OS compared with low ELNs (hazard ratio [HR] = 0.659, 95% confidence interval [CI]: 0.626-0.694, p < 0.0001). Using the training set, a nomogram incorporating ELNs was built and proven to have good calibration and discrimination (C-index [95% CI], 0.714 [0.710-0.718]), which was validated in the internal validation set (C-index [95% CI], 0.720 [0.714-0.726]), the TCGA set (C-index [95% CI], 0.693 [0.662-0.724]), and the Chinese set (C-index [95% CI], 0.750 [0.720-0.782]). An ELNs-related signature model based on ELNs group, regulatory T cells (Tregs), neutrophils, CDKN2B-AS1, H19, HOTTIP, LINC00643, MIR663AHG, TMEM236, ZNF705A, and hsa-miR-135a-5p was constructed by the LASSO-Cox regression analysis. The result showed that OS was remarkably lower in patients with high-ELNs signature compared with those with low-ELN signature (HR = 2.418, 95% CI: 1.804-3.241, p < 0.001). This signature performed well in predicting 1-, 3-, and 5-year survival (AUC [95% CI] = 0.688 [0.612-0.763], 0.744 [0.659-0.830], and 0.778 [0.647-0.909], respectively). The multivariate Cox analysis illustrated that the risk score was an independent predictor of survival for patients with GC. Moreover, the expression of prognostic genes (LINC00643, TMEM236, and hsa-miR-135a-5p) displayed differences between GC tissues and adjacent non-tumor tissues. The C-index of the nomogram that can be used to predict the OS of GC patients was 0.710 (95% CI: 0.663-0.753). Both the calibration plots and DCA showed that the nomogram has good predictive performance. Moreover, the signature was significantly correlated with the N stage and T stage. According to our analysis, GC patients in the low-ELN signature group may have a better immunotherapy response and OS outcome. CONCLUSIONS We explored the prognostic role of ELNs in GC and successfully constructed an ELNs signature linked to the GC prognosis in TCGA. The findings manifested that the signature is a powerful predictive indicator for patients with GC. The signature might contain potential biomarkers for treatment response prediction for GC patients. Additionally, we identified a novel and robust nomogram combining the characteristics of ELNs and clinical factors for predicting 1-, 3-, and 5-year OS in GC patients, which will facilitate personalized survival prediction and aid clinical decision-making in GC patients.
Collapse
Affiliation(s)
- Huling Li
- School of Public Health, Xinjiang Medical University, Urumqi, China
| | - Dandan Lin
- School of Public Health, Xinjiang Medical University, Urumqi, China
| | - Zhen Yu
- Department of Gastrointestinal Surgery, The Third Affiliated Hospital, Xinjiang Medical University, Urumqi, China
| | - Hui Li
- Central Laboratory of Xinjiang Medical University, Urumqi, China
| | - Shi Zhao
- JC School of Public Health and Primary Care, Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Tuersun Hainisayimu
- Department of Biochemistry and Molecular Biology, Basic Medicine School, Xinjiang Medical University, Urumqi, China
| | - Lin Liu
- Department of Gastrointestinal Surgery, The Third Affiliated Hospital, Xinjiang Medical University, Urumqi, China,*Correspondence: Kai Wang, ; Lin Liu,
| | - Kai Wang
- Department of Medical Engineering and Technology, Xinjiang Medical University, Urumqi, China,*Correspondence: Kai Wang, ; Lin Liu,
| |
Collapse
|
|
9
|
Significance of lncRNA CDKN2B-AS1 in Interventional Therapy of Liver Cancer and the Mechanism under Its Participation in Tumour Cell Growth via miR-199a-5p. JOURNAL OF ONCOLOGY 2022; 2022:2313416. [PMID: 36081669 PMCID: PMC9448535 DOI: 10.1155/2022/2313416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Revised: 07/07/2022] [Accepted: 07/11/2022] [Indexed: 11/17/2022]
Abstract
Methods Totally 34 LC patients admitted to our hospital between January 2020 and March 2021 (Obs group) and 32 healthy individuals over the same time span (Con group) were enrolled. CDKN2B-AS1 and miR-199a-5p in the two groups were PCR quantified, and their association and value for the diagnosis and therapy of LC were analyzed. In addition, purchased LC cells were adopted for in vitro assays, and the influences of CDKN2B-AS1 and miR-199a-5p on biological behaviours of LC cells were assessed through CCK-8, Transwell, and flow cytometry experiment, and their regulatory association was verified by the dual luciferase reporter (DLR) assay and rescue assay. And the autophagic protein expression was tested by the western blot to confirm the effect of both on the autophagic capacity of LC cells. Results CDKN2B-AS1 in LC cases presented high expression and dropped after therapy (P < 0.05), and the opposite situation of miR-199a-5p was found in the LC cases (P < 0.05). In vitro assays, after silencing of CDKN2B-AS1 and upregulation of miR-199a-5p, LC cells presented weaker viability, invasion and migration activities, and stronger apoptotic activity (all P < 0.05). The DLR assay revealed suppressed fluorescence activity of CDKN2B-AS1-WT by miR-199a-5p (P < 0.05). Moreover, according to the rescue assay, the impacts of silencing CDKN2B-AS1 on LC cells could be completely offset by silencing miR-199a-5p (P < 0.05). According to the clone formation and WB assay, the growth and autophagy of LC cells were under the regulation of CDKN2B-AS1 targeting miR-199a-5p (P < 0.05). Conclusion With high expression in LC cases, CDKN2B-AS1 is implicated in the development and progression of LC by suppressing cell autophagy through targeting miR-199a-5p.
Collapse
|
|
10
|
Wu Q, He Y, Liu X, Luo F, Jiang Y, Xiang M, Zhao R. Cancer stem cell-like cells-derived exosomal CDKN2B-AS1 stabilizes CDKN2B to promote the growth and metastasis of thyroid cancer via TGF-β1/Smad2/3 signaling. Exp Cell Res 2022; 419:113268. [PMID: 35750242 DOI: 10.1016/j.yexcr.2022.113268] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 06/14/2022] [Accepted: 06/19/2022] [Indexed: 11/30/2022]
Abstract
As CDKN2B-AS1 is demonstrated to exert promotive effects on thyroid cancer (TC), this research aims to investigate the role of cancer stem cell-like cells (CSCs)-derived exosomal CDKN2B-AS1 in TC and the underlying regulatory mechanism. Specifically, CDKN2B expression and the correlation of CDKN2B with CDKN2B-AS1 in TC were determined via bioinformatics analysis and further verified by qRT-PCR. After transfection or co-culture with CSCs-derived exosomes, viability, migration, and invasion of TPC-1 and SW579 cells were evaluated by CCK-8, wound healing, and transwell assays, respectively. The uptake of exosomes by TC cells was detected by PKH67 labeling. In vivo tumor formation and metastasis models were established. Tumor volume and weight were calculated. Metastasis loci in lung tissues were observed by hematoxylin-eosin staining. The expression levels of CDKN2B-AS1, CDKN2B, and epithelial-mesenchymal transition- and TGF-β1/Smad2/3 signaling-related factors were detected by qRT-PCR or Western blot. Concretely, CDKN2B and CDKN2B-AS1 were highly expressed in TC, and there was a positive correlation between the two. In addition, CDKN2B-AS1 promoted the translation and stability of CDKN2B. Furthermore, CDKN2B-AS1 was highly expressed in CSCs and CSCs-derived exosomes which could be absorbed by TC cells. CDKN2B silencing inhibited viability, migration, invasion, protein levels of CDKN2B, N-cadherin and Vimentin, and TGF-β1/Smad2/3 signaling, while promoting E-cadherin expression in TC cells. CSCs-derived exosomal CDKN2B-AS1 did oppositely and reversed the effects of CDKN2B silencing on TC cells. CDKN2B silencing impeded tumor growth and metastasis in TC mice, while TGF-β1 performed inversely and impaired the effects of CDKN2B silencing. Collectively, CSCs-derived exosomal CDKN2B-AS1 stabilizes CDKN2B to promote growth and metastasis of TC via TGF-β1/Smad2/3 signaling.
Collapse
Affiliation(s)
- Qinghua Wu
- Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China.
| | - Yonggang He
- Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China
| | - Xin Liu
- Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China
| | - Fangxiu Luo
- Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China
| | - Yimei Jiang
- Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China
| | - Ming Xiang
- Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China
| | - Ren Zhao
- Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China
| |
Collapse
|
|
11
|
Yang M, Yin E, Xu Y, Liu Y, Li T, Dong Z, Tai W. CDKN2B antisense RNA 1 expression alleviates idiopathic pulmonary fibrosis by functioning as a competing endogenouse RNA through the miR-199a-5p/Sestrin-2 axis. Bioengineered 2022; 13:7746-7759. [PMID: 35291918 PMCID: PMC9208479 DOI: 10.1080/21655979.2022.2044252] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Idiopathic pulmonary fibrosis (IPF) is an idiopathic interstitial lung disease. At present, the pathogenesis of IPF has not been fully elucidated, which has affected the development of effective treatment methods. Here, we explored the function and potential mechanism of long noncoding RNA (lncRNA) CDKN2B antisense RNA 1 (CDKN2B-AS1) in IPF.Transforming growth factor-β (TGF-β) and bleomycin (BLM) were used to induce IPF in cells and animal models. Real Time quantitative Polymerase Chain Reaction (RT-qPCR) showed the expression of CDKN2B-AS1, miR-199a-5p and Sestrin-2 (SESN2) in cells and tissues. The double luciferase reporter gene assay confirmed the targeting relationship among CDKN2B-AS1, miR-199a-5p, and SESN2. Related protein levels were detected by Western blot combined with Cell Counting Kit-8 (CCK-8), wound healing, and flow cytometry to analyze cell proliferation, migration, and apoptosis. The pathological characteristics of mouse lung tissue were determined by Hematoxylin-eosin (HE) and Masson staining. We found that the expression of CDKN2B-AS1 was decreased in TGF-β-treated cells and BLM-treated mice. Overexpression of CDKN2B-AS1 inhibited cell proliferation and migration, promoted apoptosis, decreased the expression of fibrosis-related proteins and promoted autophagy. In addition, overexpression of CDKN2B-AS1 alleviated pulmonary fibrosis in BLM-treated mice. Mechanistically, CDKN2B-AS1 acts as a miR-199a-5p sponge to regulate SESN2 expression. Our results indicate the importance of the CDKN2B-AS1/miR-199a-5p/SESN2 axis.
Collapse
Affiliation(s)
- Mei Yang
- Department of Respiration, The Sencond Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.,Department of Respiratory and Critical Care, Affiliated Hospital of Yunnan University, Kunming, Yunnan, China
| | - Egao Yin
- Department of Respiration, The Sencond Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Yiheng Xu
- Department of Clinical Laboratory, Yunnan Molecular Diagnostic Center, the Sencond Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Yongjun Liu
- Department of Respiration, The Sencond Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Ting Li
- Department of Respiration, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China.,Department of Respiration, Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China
| | - Zhaoxing Dong
- Department of Respiration, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China.,Department of Respiration, Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China
| | - Wenlin Tai
- Department of Clinical Laboratory, Yunnan Molecular Diagnostic Center, the Sencond Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| |
Collapse
|
|
12
|
Peng K, Xia RP, Zhao F, Xiao Y, Ma TD, Li M, Feng Y, Zhou CG. ALKBH5 promotes the progression of infantile hemangioma through regulating the NEAT1/miR-378b/FOSL1 axis. Mol Cell Biochem 2022; 477:1527-1540. [PMID: 35182329 DOI: 10.1007/s11010-022-04388-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 02/02/2022] [Indexed: 11/27/2022]
Abstract
Our work aims to investigate long non-coding RNA (lncRNA) N6-methyladenosine (m6A) modification and its role in infantile hemangioma (IH). The mRNA and protein expression levels were assessed using quantitative real-time polymerase chain reaction, western blot and immunohistochemistry. Me-RIP assay was performed to evaluate lncRNA NEAT1 m6A levels. Cell proliferation, migration and invasion were evaluated using cell counting kit-8 assay, transwell migration and invasion assay, respectively. Photo-activatable ribonucleoside-enhanced crosslinking and immunoprecipitation assay was conducted to verify the binding relationship between lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) and ALKBH5 (an RNA demethylase). The binding relationship between lncRNA NEAT1, microRNA (miR)-378b and FOS-like antigen 1 (FOSL1) was verified using dual-luciferase reporter gene assay and/or RNA immunoprecipitation assay. ALKBH5, lncRNA NEAT1 and FOLS1 expression was elevated in IH tissues, while miR-378b was downregulated. ALKBH5 knockdown suppressed cell proliferation, migration and invasion of IH cells, while promoting cell apoptosis. ALKBH5 promoted lncRNA NEAT1 expression by reducing the m6A modification of lncRNA NEAT1. In addition, miR-378b was the target of lncRNA NEAT1, and its overexpression reversed the promotion effect of lncRNA NEAT1 overexpression on IH cell tumor-like behaviors. Moreover, FOLS1 was the target of miR-378b, and its overexpression reversed the inhibitory effect of miR-378b overexpression on IH cell tumor-like behaviors in vitro. ALKBH5 might have great potential as therapeutic target for IH, since ALKBH5 silencing suppressed IH progression by regulation of the NEAT1/miR-378b/FOSL1 axis.
Collapse
Affiliation(s)
- Kun Peng
- Department of Fetal and Neonatal Surgery, Hunan Children's Hospital, No.86, Ziyuan Road, Yuhua District, Changsha, 410007, Hunan, People's Republic of China
| | - Ren-Peng Xia
- Department of Fetal and Neonatal Surgery, Hunan Children's Hospital, No.86, Ziyuan Road, Yuhua District, Changsha, 410007, Hunan, People's Republic of China
| | - Fan Zhao
- Department of Fetal and Neonatal Surgery, Hunan Children's Hospital, No.86, Ziyuan Road, Yuhua District, Changsha, 410007, Hunan, People's Republic of China
| | - Yong Xiao
- Department of Fetal and Neonatal Surgery, Hunan Children's Hospital, No.86, Ziyuan Road, Yuhua District, Changsha, 410007, Hunan, People's Republic of China
| | - Ti-Dong Ma
- Department of Fetal and Neonatal Surgery, Hunan Children's Hospital, No.86, Ziyuan Road, Yuhua District, Changsha, 410007, Hunan, People's Republic of China
| | - Ming Li
- Department of Fetal and Neonatal Surgery, Hunan Children's Hospital, No.86, Ziyuan Road, Yuhua District, Changsha, 410007, Hunan, People's Republic of China
| | - Yong Feng
- Department of Fetal and Neonatal Surgery, Hunan Children's Hospital, No.86, Ziyuan Road, Yuhua District, Changsha, 410007, Hunan, People's Republic of China
| | - Chong-Gao Zhou
- Department of Fetal and Neonatal Surgery, Hunan Children's Hospital, No.86, Ziyuan Road, Yuhua District, Changsha, 410007, Hunan, People's Republic of China.
| |
Collapse
|
|
13
|
Qin S, Ning M, Liu Q, Ding X, Wang Y, Liu Q. Knockdown of long non-coding RNA CDKN2B-AS1 suppresses the progression of breast cancer by miR-122-5p/STK39 axis. Bioengineered 2021; 12:5125-5137. [PMID: 34374638 PMCID: PMC8806778 DOI: 10.1080/21655979.2021.1962685] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 07/26/2021] [Accepted: 07/27/2021] [Indexed: 02/07/2023] Open
Abstract
The lncRNAs have been made certain to take part in the development of most cancers in multiple ways. Here, our purpose is to making observation of the biological role and function of lncRNA CDKN2B-AS1 in human breast cancer. Twenty-eight pairs of breast cancer tissue and adjacent normal tissue from breast cancer patients were used to investigate the expression of CDKN2B-AS1 by qRT-PCR. And a lentivirus-shRNA guided CDKN2B-AS1 were to reduce its expression. The function of CDKN2B-AS1 was analyzed using a series of in vitro assays. Meanwhile, the xenograft model was used to further explicate the role of CDKN2B-AS1 in breast cancer. As for the results, there is a relative rich expression of CDKN2B-AS1 in breast cancer tissues compared with the corresponding adjacent normal tissues. Compared with the human breast epithelial cell line, the abundant expression of CDKN2B-AS1 in breast cancer cells were revealed as well. Then, knockdown CDKN2B-AS1 inhibited the malignant biological behaviors of MCF7 and T47D cells. In mechanism, CDKN2B-AS1 sponged the miR-122-5p to regulate STK39 expression. Furthermore, the inhibition effect with sh-CDKN2B-AS1 on breast cancer cells was alleviated by miR-122-5p inhibitor. Last, an in vivo model also confirmed that knockdown CDKN2B-AS1 retarded the growth of breast cancer. Our data concluded that knockdown of CDKN2B-AS1 suppresses the progression of breast cancer by miR-122-5p/STK39 axis.
Collapse
Affiliation(s)
- Shaojie Qin
- The Third Departments of Tumor Surgery, General Hospital of Ningxia Medical University, Yinchuan City, Ningxia, China
| | - Mingliang Ning
- The Third Departments of Tumor Surgery, General Hospital of Ningxia Medical University, Yinchuan City, Ningxia, China
| | - Qingyuan Liu
- The Third Departments of Tumor Surgery, General Hospital of Ningxia Medical University, Yinchuan City, Ningxia, China
| | - Xiaoyun Ding
- The Third Departments of Tumor Surgery, General Hospital of Ningxia Medical University, Yinchuan City, Ningxia, China
| | - Yanbai Wang
- Cerebrospinal Fluid Laboratory; General Hospital of Ningxia Medical University, Yinchuan City, Ningxia, China
| | - Qilun Liu
- The Third Departments of Tumor Surgery, General Hospital of Ningxia Medical University, Yinchuan City, Ningxia, China
| |
Collapse
|
|
14
|
Yang D, Ma J, Ma XX. CDKN2B-AS1 Promotes Malignancy as a Novel Prognosis-Related Molecular Marker in the Endometrial Cancer Immune Microenvironment. Front Cell Dev Biol 2021; 9:721676. [PMID: 34712660 PMCID: PMC8546264 DOI: 10.3389/fcell.2021.721676] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Accepted: 09/17/2021] [Indexed: 11/25/2022] Open
Abstract
The prognosis of patients with endometrial cancer (EC) is closely associated with immune cell infiltration. Although abnormal long non-coding RNA (lncRNA) expression is also linked to poor prognosis in patients with EC, the function and action mechanism of immune infiltration-related lncRNAs underlying the occurrence and development of EC remains unclear. In this study, we analyzed lncRNA expression using The Cancer Genome Atlas and clinical data and identified six lncRNAs as prognostic markers for EC, all of which are associated with the infiltration of immune cell subtypes, as illustrated by ImmLnc database and ssGSEA analysis. Real-time quantitative polymerase chain reaction showed that CDKN2B-AS1 was significantly overexpressed in EC, whereas its knockdown inhibited the proliferation and invasion of EC cells and the in vivo growth of transplanted tumors in nude mice. Finally, we constructed a competing endogenous RNA regulatory network and conducted Gene Ontology enrichment analysis to elucidate the potential molecular mechanism underlying CDKN2B-AS1 function. Overall, we identified molecular targets associated with immune infiltration and prognosis and provide new insights into the development of molecular therapies and treatment strategies against EC.
Collapse
Affiliation(s)
- Di Yang
- Department of Gynecology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China
| | - Jian Ma
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xiao-Xin Ma
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| |
Collapse
|
|
15
|
Saliani M, Mirzaiebadizi A, Mosaddeghzadeh N, Ahmadian MR. RHO GTPase-Related Long Noncoding RNAs in Human Cancers. Cancers (Basel) 2021; 13:5386. [PMID: 34771549 PMCID: PMC8582479 DOI: 10.3390/cancers13215386] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Revised: 10/21/2021] [Accepted: 10/22/2021] [Indexed: 12/27/2022] Open
Abstract
RHO GTPases are critical signal transducers that regulate cell adhesion, polarity, and migration through multiple signaling pathways. While all these cellular processes are crucial for the maintenance of normal cell homeostasis, disturbances in RHO GTPase-associated signaling pathways contribute to different human diseases, including many malignancies. Several members of the RHO GTPase family are frequently upregulated in human tumors. Abnormal gene regulation confirms the pivotal role of lncRNAs as critical gene regulators, and thus, they could potentially act as oncogenes or tumor suppressors. lncRNAs most likely act as sponges for miRNAs, which are known to be dysregulated in various cancers. In this regard, the significant role of miRNAs targeting RHO GTPases supports the view that the aberrant expression of lncRNAs may reciprocally change the intensity of RHO GTPase-associated signaling pathways. In this review article, we summarize recent advances in lncRNA research, with a specific focus on their sponge effects on RHO GTPase-targeting miRNAs to crucially mediate gene expression in different cancer cell types and tissues. We will focus in particular on five members of the RHO GTPase family, including RHOA, RHOB, RHOC, RAC1, and CDC42, to illustrate the role of lncRNAs in cancer progression. A deeper understanding of the widespread dysregulation of lncRNAs is of fundamental importance for confirmation of their contribution to RHO GTPase-dependent carcinogenesis.
Collapse
Affiliation(s)
- Mahsa Saliani
- Institute of Biochemistry and Molecular Biology II, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine University, 40225 Düsseldorf, Germany
- Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad 9177948974, Iran
| | - Amin Mirzaiebadizi
- Institute of Biochemistry and Molecular Biology II, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine University, 40225 Düsseldorf, Germany
| | - Niloufar Mosaddeghzadeh
- Institute of Biochemistry and Molecular Biology II, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine University, 40225 Düsseldorf, Germany
| | - Mohammad Reza Ahmadian
- Institute of Biochemistry and Molecular Biology II, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine University, 40225 Düsseldorf, Germany
| |
Collapse
|
|
16
|
Zhao Z, Li G, Han Y, Li Y, Ji Z, Guo R, Yu X. Circular RNA ZNF609 enhances proliferation and glycolysis during glioma progression by miR-378b/SLC2A1 axis. Aging (Albany NY) 2021; 13:21122-21133. [PMID: 34520391 PMCID: PMC8457557 DOI: 10.18632/aging.203331] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 07/09/2021] [Indexed: 01/01/2023]
Abstract
Glioma is a prevalent brain malignancy with aggressive progression and with grave prognosis in adults. Circular RNAs have been reported to regulate glioma development and function as the diagnostic, prognostic, and therapeutic biomarkers. In this study, we were interested the function of circular RNA ZNF609 in modulating glioma. Remarkably, knockdown of ZNF609 by siRNA in glioma cells reduced cell viabilities and Edu-positive. The silencing of ZNF609 stimulated the apoptosis of glioma cells. Meanwhile, the ZNF609 depletion inhibited the invasion and migration of glioma cells. In glioma cells, the mRNA and protein expression of E-cadherin was enhanced, while Vimentin was reduced by the inhibition of ZNF609. The glucose uptake, lactate product, and ATP production in glioma cells were suppressed by ZNF609 knockdown. Mechanically, miR-378b was sponged by ZNF609 and targeted SLC2A1 in glioma cells. ZNF609 enhanced SLC2A1 expression by inhibiting miR-378b. The inhibition of miR-378b or the enhancement of SLC2A1 reversed ZNF609 depletion-regulated glioma cell proliferation in vitro. The depletion of ZNF609 suppressed glioma cell growth in the nude mice. Therefore, we concluded that ZNF609 contributed to cell survival and glycolysis of glioma by targeting miR-378b/SLC2A1 axis. ZNF609 and miR-378b may function as potential treatment targets in glioma.
Collapse
Affiliation(s)
- Zhihuang Zhao
- Third Department of Neurosurgery, Cangzhou Central Hospital, Cangzhou, Hebei, China
| | - Gang Li
- Third Department of Neurosurgery, Cangzhou Central Hospital, Cangzhou, Hebei, China
| | - Yonggang Han
- Third Department of Neurosurgery, Cangzhou Central Hospital, Cangzhou, Hebei, China
| | - Yabin Li
- Third Department of Neurosurgery, Cangzhou Central Hospital, Cangzhou, Hebei, China
| | - Zhisheng Ji
- Third Department of Neurosurgery, Cangzhou Central Hospital, Cangzhou, Hebei, China
| | - Rui Guo
- Bozhou Baozhang Hospital, Haozhou, Anhui Province, China
| | - Xiaohong Yu
- Department of Urology Surgery, Linyi People's Hospital, Linyi, Shandong Province, China
| |
Collapse
|
|
17
|
Son SW, Yun BD, Song MG, Lee JK, Choi SY, Kuh HJ, Park JK. The Hypoxia-Long Noncoding RNA Interaction in Solid Cancers. Int J Mol Sci 2021; 22:ijms22147261. [PMID: 34298879 PMCID: PMC8307739 DOI: 10.3390/ijms22147261] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 06/29/2021] [Accepted: 07/01/2021] [Indexed: 02/07/2023] Open
Abstract
Hypoxia is one of the representative microenvironment features in cancer and is considered to be associated with the dismal prognosis of patients. Hypoxia-driven cellular pathways are largely regulated by hypoxia-inducible factors (HIFs) and notably exert influence on the hallmarks of cancer, such as stemness, angiogenesis, invasion, metastasis, and the resistance towards apoptotic cell death and therapeutic resistance; therefore, hypoxia has been considered as a potential hurdle for cancer therapy. Growing evidence has demonstrated that long noncoding RNAs (lncRNAs) are dysregulated in cancer and take part in gene regulatory networks owing to their various modes of action through interacting with proteins and microRNAs. In this review, we focus attention on the relationship between hypoxia/HIFs and lncRNAs, in company with the possibility of lncRNAs as candidate molecules for controlling cancer.
Collapse
Affiliation(s)
- Seung Wan Son
- Department of Biomedical Science, Research Institute for Bioscience & Biotechnology, Hallym University, Chunchon 24252, Korea; (S.W.S.); (B.D.Y.); (M.G.S.); (J.K.L.); (S.Y.C.)
| | - Ba Da Yun
- Department of Biomedical Science, Research Institute for Bioscience & Biotechnology, Hallym University, Chunchon 24252, Korea; (S.W.S.); (B.D.Y.); (M.G.S.); (J.K.L.); (S.Y.C.)
| | - Mun Gyu Song
- Department of Biomedical Science, Research Institute for Bioscience & Biotechnology, Hallym University, Chunchon 24252, Korea; (S.W.S.); (B.D.Y.); (M.G.S.); (J.K.L.); (S.Y.C.)
| | - Jin Kyeong Lee
- Department of Biomedical Science, Research Institute for Bioscience & Biotechnology, Hallym University, Chunchon 24252, Korea; (S.W.S.); (B.D.Y.); (M.G.S.); (J.K.L.); (S.Y.C.)
| | - Soo Young Choi
- Department of Biomedical Science, Research Institute for Bioscience & Biotechnology, Hallym University, Chunchon 24252, Korea; (S.W.S.); (B.D.Y.); (M.G.S.); (J.K.L.); (S.Y.C.)
| | - Hyo Jeong Kuh
- Department of Medical Life Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea;
| | - Jong Kook Park
- Department of Biomedical Science, Research Institute for Bioscience & Biotechnology, Hallym University, Chunchon 24252, Korea; (S.W.S.); (B.D.Y.); (M.G.S.); (J.K.L.); (S.Y.C.)
- Correspondence: ; Tel.: +82-33-248-2114
| |
Collapse
|
|
18
|
Chen Q, Guo H, Zong Y, Zhao X. Curcumin restrains hepatocellular carcinoma progression depending on the regulation of the circ_0078710/miR-378b/PRIM2 axis. J Recept Signal Transduct Res 2021; 42:313-324. [PMID: 34139933 DOI: 10.1080/10799893.2021.1936554] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
PURPOSE Curcumin has shown anti-tumor activity in multiple malignancies. The aim of our study was to explore the molecular mechanism behind the anti-tumor activity of curcumin in hepatocellular carcinoma (HCC). METHODS The proliferation, migration, invasion, and apoptosis were analyzed by 5-ethynyl-2'-deoxyuridine (EDU) assay, transwell migration assay, transwell invasion assay, and flow cytometry. Western blot assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were conducted to analyze protein and RNA expression. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RNA-pull down assay were performed to confirm the interaction between microRNA-378b (miR-378b) and circular RNA_0078710 (circ_0078710) or DNA primase, polypeptide 2 (PRIM2). Tumor xenograft assay was conducted to assess the roles of curcumin and circ_0078710 in vivo. RESULTS Curcumin stimulation restrained the proliferation, migration, and invasion, and triggered the apoptosis of HCC cells. Curcumin down-regulated the expression of circ_0078710 in HCC cells in a dose-dependent manner. Circ_0078710 knockdown aggravated curcumin-mediated anti-tumor effects in HCC cells. Circ_0078710 acted as a molecular sponge for miR-378b. Circ_0078710 interference-induced effects in curcumin-stimulated HCC cells were partly abolished by the silence of miR-378b. MiR-378b bound to the 3' untranslated region (3'UTR) of PRIM2. PRIM2 overexpression partly reversed circ_0078710 interference-mediated influences in curcumin-treated HCC cells. Circ_0078710 silencing aggravated curcumin-mediated suppressive effect in tumor growth in vivo. CONCLUSIONS Circ_0078710 silencing aggravated curcumin-mediated anti-tumor effects through mediating the miR-378b/PRIM2 signaling in HCC cells.
Collapse
Affiliation(s)
- Qian Chen
- Department of Traditional Chinese Medicine, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian City, Jiangsu Province, China
| | - Hai Guo
- Department of Traditional Chinese Medicine, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian City, Jiangsu Province, China
| | - Yan Zong
- Department of Traditional Chinese Medicine, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian City, Jiangsu Province, China
| | - Xiaofeng Zhao
- Department of Traditional Chinese Medicine, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian City, Jiangsu Province, China
| |
Collapse
|