Microrna-146a-5p Enhances Cisplatin-Induced Apoptosis In Ovarian Cancer Cells By Targeting Multiple Anti-Apoptotic Genes

MicroRNAs play a crucial role in gene expression regulation in various types of cancers. Previous studies show the expression level of miR-146a-5p is downregulated in epithelial ovarian cancer. Further investigations suggest this downregulation is responsible for apoptosis resistance in ovarian cancer cells. However, the mechanism of how miR-146a-5p promotes apoptosis remains unclear. In this study, the role of miR-146a-5p in cisplatin-induced apoptosis of ovarian cancer cells was assessed by DAPI staining, MTT assays, and monitoring expression of XIAP, BCL2L2, BIRC2 and BIRC5 through a dual-luciferase assay. Our results show that miR-146a-5p can regulate three important anti-apoptotic genes including XIAP, BCL2L2 and BIRC5 via their 3'UTRs. Not only can overexpression of miR-146a-5p downregulate the expression of XIAP in SKOV3 cells, but it also lowers the IC50 values of cisplatin in OVCAR3 and SKOV3 cells and enhances the susceptibility of OVCAR3, SKOV3 and primary ovarian cancer cells to cisplatin-induced apoptosis. The effect of XIAP rescuing cisplatin-induced apoptosis accelerated by miR-146a-5p further supports our conclusion. Our results suggest that the regulation of three anti-apoptotic genes by miR-146-5p enhances the therapeutic effects of cisplatin.