Study of molecular mechanism of miR-34c in the inhibition of endometrial carcinoma

Objective MicroRNAs(miRNAs) are endogenously expressed 22-nucleotide small RNAs which repress protein translation through binding to a target mRNA. The recent studies have shown that some miRNAs can regulate proliferation and migration of tumor cells. The role of miRNAs in endometrial carcinoma,however,warrants for further investigation. In the present study,we investigated miR-34 c expression pattern,function and molecular mechanism in endometrial carcinoma. Methods Real-time RT-PCR was performed to detect the expression of miR-34 c in 20 endometrial carcinoma specimens. The miR-34 c was transfected into RL95-2 cells by using lipofectamine reagent. The proliferation of RL95-2cells was examined by MTS cell proliferation assay and colony formation assay. The cell cycle was analyzed by flow cytometry and cell migration was evaluated by Transwell assay. The target of miR-34 c was predicted by bioinformatics and confirmed by luciferase assay. C-Met was down-regulated by RNAi. Western blot analysis was carried out to examine the effects of miR-34 c on c-Met and proteins in important cellular signaling pathways. Results MiR-34 c was dramatically down-regulated in most endometrial carcinoma samples. Ectopic miR-34 c can inhibit the proliferation of RL95-2 cells through cell cycle G1 arrest. Furthermore,miR-34 c suppressed RL95-2 cell migration. Bioinformatics revealed c-Met was a target gene of miR-34 c and confirmed by luciferase assay. Western blot analysis indicated that miR-34 c down-regulated the expression of c-Met,p-Akt,p-ERK1/2,CDK4,CDK6 and p-Rb. Conclusion The miR-34 c can inhibite endometrial carcinoma cell proliferation and migration by targeting c-Met,which indicates that miR-34 c may act as an important tumor suppressor in ndometrial carcinoma.