Ovarian cancer (OvCa) is the third most common female malignancy worldwide and poses great threats on women health. Chemotherapy is the most recommended post-surgery treatment for OvCa patients; but, cisplatin resistance is a main cause of chemotherapy failure. In addition, autophagy modulates the sensitivity of tumor cells to chemotherapeutic agents. Hence, it is significant to explore the molecular mechanism concerning the autophagy and cisplatin resistance in OvCa. In this study, quantitative real-time PCR (qRT-PCR) was used to detect miR-20a-5p expression and western blot to measure RBP1 expression. A series of assays were conducted to explore the gain-of-function effects of miR-20a-5p. Luciferase reporter assay was applied to determine the downstream target of miR-20a-5p. The results proved that miR-20a-5p represses malignant phenotypes and autophagy in cisplatin-resistant OvCa cells. In addition, DNMT3B mediates DNA methylation of RBP1 to impair the promoting effects of RBP1 on carcinogenesis and autophagy in OvCa. Through rescue experiments, we certified that miR-20a-5p inhibits the autophagy and cisplatin resistance in OvCa via DNMT3B-mediated DNA methylation of RBP1. Collectively, we demonstrated that miR-20a-5p plays a crucial role in the modulation of autophagy and cisplatin resistance in OvCa, which might offer novel insights into developing effective treatment strategies for OvCa.
Keywords: DNMT3B; MicroRNA-20a-5p; Ovarian cancer; RBP1.
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