Objective: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
Keywords: Cisplatin resistance; Ovarian cancer; hMSH2; miR-590-5p.
© 2023. The Author(s), under exclusive licence to Springer Nature B.V.