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.

基于顺铂 (DDP) 的策略是癌症的一线治疗；然而，对 DDP 的耐药性仍然是癌症治疗的主要障碍。目前的研究旨在研究 microRNA-181c (miR-181c) 对卵巢癌细胞对 DDP 抗性的影响。使用基于微阵列的分析筛选卵巢癌相关 miR 以及靶信使 RNA，然后通过 RT-qPCR 和蛋白质印迹分析确定卵巢癌组织中 miR-181c 和中胚层特异性转录物 (MEST) 的表达模式。随后，进行双荧光素酶报告基因检测以确认 miR-181c 和 MEST 之间的靶向关系。通过获得或失去功能的实验，该研究探讨了miR-181通过Wnt/β-catenin信号通路调节MEST影响卵巢癌细胞对DDP耐药的机制。随后，从骨髓基质细胞（BMSCs）中分离出细胞外囊泡（EVs）并与卵巢癌细胞共培养，以进一步研究BMSCs衍生的EVs传递过表达的miR-181对卵巢癌细胞对DDP耐药的影响。miR-181c 显着下调，而 MEST 在卵巢癌中上调。miR-181c 被证实与 MEST 特异性结合。过表达的 miR-181c 通过使 Wnt/β-catenin 信号通路失活，耗尽了 MEST 的表达，从而减弱了卵巢癌细胞对 DDP 的抗性。此外，发现由 BMSCs 衍生的 EV 传递过表达的 miR-181c 可抑制卵巢癌细胞对 DDP 的抗性。这些发现表明，由 BMSCs 衍生的 EVs 传递的 miR-181c 下调 MEST，使 Wnt/β-catenin 信号通路失活，从而抑制卵巢癌细胞对 DDP 的抗性。