miR-509-3p enhances platinum drug sensitivity in ovarian cancer.

Drug-resistance of platinum remains a big challenge for effective treatment of patients with ovarian cancer. MicroRNAs (miRNAs) act as post-transcriptional regulators of gene expression and are associated with multi-drug resistance. Our study aims on identifying role of miRNAs in drug-resistance of platinum in ovarian cancer. In present study, we compared the expression profiles of miRNAs between three pairs of platinum-resistant and platinum-sensitive ovarian tissues and found that miR-509-3p was significantly down-regulated in cisplatin-resistant ovarian cancer tissues. The different expression of miR-509-3p was further determined by RT-qPCR analyses of tissue samples from groups of 20 patients with cisplatin-sensitive ovarian cancer and 7 patients with cisplatin-resistant ovarian cancer. Functional studies demonstrated that miR-509-3p inhibitor decreased cell response to cisplatin (CDDP) and promoted cell survival in SKOV3 ovarian cancer cells. Furthermore, we found gene expression level of Golgi phosphoprotein-3 (GOLPH3) and wntless Wnt ligand secretion mediator (WLS) were regulated by miR-509-3p. The direct bindings of miR-509-3p to GOLPH3 and WLS genes were confirmed by dual-luciferase reporter assay. And the negative correlation between their expression levels in SKOV3 cells was further verified with RT-qPCR. Altogether, our data provide preliminary evidence, supporting that targeting miR-509-3p might be a potential therapeutic strategy for patients with platinum-resistant ovarian cancer.

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