MiR-590-5p promotes cisplatin resistance via targeting hMSH2 in ovarian cancer.

Abstract

The mechanisms of ovarian cancer generate chemotherapy resistance are still unclear. This study aimed to explore the role of microRNA (miR)-590-5p in regulating hMSH2 expression and cisplatin resistance in ovarian cancer. MiR-590-5p was identified as a regulator of hMSH2 with miRDB database and Target Scan database. Then cisplatin sensitive cell line (SKOV3) and resistant cell line (SKOV3-DDP) of ovarian cancer were cultured for cell functional assay and molecular biology assay. The expression levels of MiR-590-5p and hMSH2 were compared between the two cell lines. Dual luciferase reporter assay was used to verify the targeted regulatory relationship between miR-590-5p and hMSH2. CCK-8 assay and cell apoptosis assay were utilized to assess the role of MiR-590-5p and hMSH2 in cell viability under cisplatin. The expression of hMSH2 was significantly decreased, and miR-590-5p was significantly up-regulated in SKOV3-DDP. Up-regulation of hMSH2 weakened the viability of SKOV3 and SKOV3-DDP cell under cisplatin. Transfection with miR‑590-5p mimics reduced the expression of hMSH2 and enhanced the viability of ovarian cancer cells under cisplatin, whereas inhibition of miR‑590-5p increased the expression of hMSH2, and decreased ovarian cancer cells' viability under cisplatin. Furthermore, luciferase reporter assay showed that hMSH2 was a direct target of miR-590-5p. The present study demonstrates that miR‑590-5p promotes cisplatin resistance of ovarian cancer via negatively regulating hMSH2 expression. Inhibition of miR‑590-5p decreases ovarian cancer cells' viability under cisplatin. Thus miR‑590-5p and hMSH2 may serve as therapeutic targets for cisplatin resistant ovarian cancer.