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MicroRNA-145 targets TRIM2 and exerts tumor-suppressing functions in epithelial ovarian cancer.
Gynecol Oncol. 2015 Dec; 139(3):513-9.GO

Abstract

OBJECTIVE

Epithelial ovarian cancer (EOC) is one of the most common cancers in women worldwide but relatively little is known about its molecular pathogenesis. MicroRNAs, which regulate gene expression post-transcriptionally, have emerged as key players in tumorigenesis. The present study aims to investigate the dysregulation of miR-145 in EOC.

METHODS

miRNA expression was assessed in EOC tissues and cell lines by quantitative reverse transcription (RT)-PCR. Xenograft mouse model was used for evaluation of the effect of miR-145 on tumor growth. Cell proliferation, colony formation assays, invasion assay, flow cytometry, Western blot and gene expression analysis were used for identification of the functional role of miR-145 in EOC cells. Luciferase reporter assay was used to confirm the interaction between miR-145 and its target mRNA 3'-UTR.

RESULTS

miR-145 expression was downregulated in EOC tissues and cell lines as compared with normal ovarian tissues. Transfection of miR-145 agomiR significantly inhibited the proliferation, colony forming ability, invasiveness and in vivo tumorigenicity of EOC cells. Transfection of agomiR-145 into EOC cells also markedly induced apoptosis. Furthermore, computational algorithm combined with luciferase reporter assays identified TRIM2 as the direct target of miR-145 in EOC cells. To this end, agomiR-145 downregulated TRIM2 to derepress Bim (a pro-apoptotic Bcl-2 family member degraded by TRIM2).

CONCLUSIONS

These data confirmed the tumor-suppressing function of miR-145 in EOC and identified TRIM2 as a new miR-145 target. In vivo delivery of agomiR-145 might be a feasible approach for miRNA-directed cancer therapy.

Authors+Show Affiliations

Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang 212013, China.Institute of Molecular Ecology and Evolution, East China Normal University, Shanghai 200062, China. Electronic address: cgdong@bio.ecnu.edu.cn.Department of Microbiology, The Chinese University of Hong Kong, Hong Kong, China.Department of Anaesthesia and Intensive Care and State Key Laboratory of Digestive Disease, LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang 212013, China.Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang 212013, China.Department of Anaesthesia and Intensive Care and State Key Laboratory of Digestive Disease, LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China. Electronic address: wukakei@cuhk.edu.hk.Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang 212013, China. Electronic address: xuhx@ujs.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26472353

Citation

Chen, Xiaobo, et al. "MicroRNA-145 Targets TRIM2 and Exerts Tumor-suppressing Functions in Epithelial Ovarian Cancer." Gynecologic Oncology, vol. 139, no. 3, 2015, pp. 513-9.
Chen X, Dong C, Law PT, et al. MicroRNA-145 targets TRIM2 and exerts tumor-suppressing functions in epithelial ovarian cancer. Gynecol Oncol. 2015;139(3):513-9.
Chen, X., Dong, C., Law, P. T., Chan, M. T., Su, Z., Wang, S., Wu, W. K., & Xu, H. (2015). MicroRNA-145 targets TRIM2 and exerts tumor-suppressing functions in epithelial ovarian cancer. Gynecologic Oncology, 139(3), 513-9. https://doi.org/10.1016/j.ygyno.2015.10.008
Chen X, et al. MicroRNA-145 Targets TRIM2 and Exerts Tumor-suppressing Functions in Epithelial Ovarian Cancer. Gynecol Oncol. 2015;139(3):513-9. PubMed PMID: 26472353.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MicroRNA-145 targets TRIM2 and exerts tumor-suppressing functions in epithelial ovarian cancer. AU - Chen,Xiaobo, AU - Dong,Changgui, AU - Law,Priscilla T Y, AU - Chan,Matthew T V, AU - Su,Zhaoliang, AU - Wang,Shengjun, AU - Wu,William K K, AU - Xu,Huaxi, Y1 - 2015/10/16/ PY - 2015/07/14/received PY - 2015/10/05/revised PY - 2015/10/10/accepted PY - 2015/10/17/entrez PY - 2015/10/17/pubmed PY - 2016/4/14/medline KW - Apoptosis KW - Epithelial ovarian cancer KW - MicroRNA KW - Trim2 KW - Tumor-suppressor SP - 513 EP - 9 JF - Gynecologic oncology JO - Gynecol. Oncol. VL - 139 IS - 3 N2 - OBJECTIVE: Epithelial ovarian cancer (EOC) is one of the most common cancers in women worldwide but relatively little is known about its molecular pathogenesis. MicroRNAs, which regulate gene expression post-transcriptionally, have emerged as key players in tumorigenesis. The present study aims to investigate the dysregulation of miR-145 in EOC. METHODS: miRNA expression was assessed in EOC tissues and cell lines by quantitative reverse transcription (RT)-PCR. Xenograft mouse model was used for evaluation of the effect of miR-145 on tumor growth. Cell proliferation, colony formation assays, invasion assay, flow cytometry, Western blot and gene expression analysis were used for identification of the functional role of miR-145 in EOC cells. Luciferase reporter assay was used to confirm the interaction between miR-145 and its target mRNA 3'-UTR. RESULTS: miR-145 expression was downregulated in EOC tissues and cell lines as compared with normal ovarian tissues. Transfection of miR-145 agomiR significantly inhibited the proliferation, colony forming ability, invasiveness and in vivo tumorigenicity of EOC cells. Transfection of agomiR-145 into EOC cells also markedly induced apoptosis. Furthermore, computational algorithm combined with luciferase reporter assays identified TRIM2 as the direct target of miR-145 in EOC cells. To this end, agomiR-145 downregulated TRIM2 to derepress Bim (a pro-apoptotic Bcl-2 family member degraded by TRIM2). CONCLUSIONS: These data confirmed the tumor-suppressing function of miR-145 in EOC and identified TRIM2 as a new miR-145 target. In vivo delivery of agomiR-145 might be a feasible approach for miRNA-directed cancer therapy. SN - 1095-6859 UR - https://www.unboundmedicine.com/medline/citation/26472353/MicroRNA_145_targets_TRIM2_and_exerts_tumor_suppressing_functions_in_epithelial_ovarian_cancer_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0090-8258(15)30157-8 DB - PRIME DP - Unbound Medicine ER -