title: MicroRNA-145 targets TRIM2 and exerts tumor-suppressing functions in epithelial ovarian cancer.
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.affiliation: Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang 212013, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Chen
authors.affiliation: Institute of Molecular Ecology and Evolution, East China Normal University, Shanghai 200062, China. Electronic address: cgdong@bio.ecnu.edu.cn.
authors.forename: Changgui
authors.initials: C
authors.lastname: Dong
authors.affiliation: Department of Microbiology, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Priscilla T Y
authors.initials: PT
authors.lastname: Law
authors.affiliation: 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.
authors.forename: Matthew T V
authors.initials: MT
authors.lastname: Chan
authors.affiliation: Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang 212013, China.
authors.forename: Zhaoliang
authors.initials: Z
authors.lastname: Su
authors.affiliation: Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang 212013, China.
authors.forename: Shengjun
authors.initials: S
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: William K K
authors.initials: WK
authors.lastname: Wu
authors.affiliation: Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang 212013, China. Electronic address: xuhx@ujs.edu.cn.
authors.forename: Huaxi
authors.initials: H
authors.lastname: Xu
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000502:physiology*; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D010053:Ovary / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection; D014410:Tumor Stem Cell Assay
chemical_list: D020413:3' Untranslated Regions; D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; C541010:MIRN145 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; C400022:NARF protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger
keywords: Apoptosis; Epithelial ovarian cancer; MicroRNA; Trim2; Tumor-suppressor