Abstract
Cisplatin (DDP)-based strategies are the first-line treatment for cancers; however, resistance to DDP remains a major obstacle to cancer treatment. The current study set out to investigate the effects of microRNA-181c (miR-181c) on the resistance of ovarian cancer cells to DDP. Ovarian cancer-associated miRs as well as the target messenger RNAs were screened using microarray-based analysis followed by determining the expression patterns of miR-181c and mesoderm-specific transcript (MEST) in ovarian cancer tissues with RT-qPCR and Western blot analysis. Subsequently, dual-luciferase reporter gene assay was performed to confirm the targeting relation between miR-181c and MEST. Through gain- or loss-of-function experiments, the study explored the mechanism by which miR-181 regulated MEST to influence the resistance of ovarian cancer cells to DDP via the Wnt/β-catenin signaling pathway. Afterwards, extracellular vesicles (EVs) were isolated from bone marrow stromal cells (BMSCs) and co-cultured with ovarian cancer cells to further investigate the effects of overexpressed miR-181 delivered by BMSCs-derived EVs on ovarian cancer cell resistance to DDP. miR-181c was significantly downregulated, while MEST was up-regulated in ovarian cancer. miR-181c was verified to specifically bind to MEST. Overexpressed miR-181c depleted the expression of MEST to attenuate the resistance of ovarian cancer cells to DDP by inactivating the Wnt/β-catenin signaling pathway. Furthermore, the delivery of overexpressed miR-181c by BMSCs-derived EVs was found to suppress the resistance of ovarian cancer cells to DDP. These findings demonstrate that miR-181c delivered by BMSCs-derived EVs down-regulates MEST, to inactivate the Wnt/β-catenin signaling pathway, thus repressing the resistance of ovarian cancer cells to DDP.