MicroRNA-145 targets TRIM2 and exerts tumor-suppressing functions in epithelial ovarian cancer.

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.