Exosomes carrying microRNAs (miRNAs) have been demonstrated to play critical roles in the regulation of development, growth and metastasis of cancer. Bioinformatic predictions identified differentially expressed SRY-box 9 (SOX9) in OC, and the regulatory miRNA miR-139-5p. Here, we aim to evaluate the function of exosomal miR-139-5p in the sensitivity of ovarian cancer (OC) cells to cis-diamminedichloroplatinum(II) (DDP). Expression pattern of miR-139-5p and SOX9 in ovarian cancer cells (SKOV3) and DDP-resistant cells (SKOV3/DDP) was identified using reverse transcription quantitative polymerase chain reaction and western blot analysis. The relationship between miR-139-5p and SOX9 was validated using a dual-luciferase reporter assay. SKOV3/DDP cell line was developed and introduced with miR-30a-5p mimic to analyse the effects of miR-30a-5p on resistance to DDP. The in vitro and in vivo effects of exosomal miR-30a-5p on resistance of SKOV3 cells to DDP were assessed in a co-culture system of exosomes and OC cells as well as in tumour-bearing nude mice. High expression of SOX9 and low expression of miR-30-5p were witnessed in OC. Furthermore, miR-30-5p, a downregulated miRNA in SKOV3/DDP cells, increased the rate of cell apoptosis and enhanced the sensitivity of SKOV3/DDP cells to DDP by targeting SOX9. Moreover, exosomes carrying miR-30a-5p were identified to sensitize SKOV3/DDP cells to DDP both in vitro and in vivo. These data together supported an important conclusion that DDP-resistant OC cell-derived exosomal miR-30a-5p enhanced cellular sensitivity to DDP, highlighting a potential strategy to overcome drug resistance.

中文翻译：

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DDP抗性卵巢癌细胞衍生的外泌体microRNA-30a-5p降低卵巢癌细胞对DDP的抗性。

携带微小RNA（miRNA）的外泌体已被证明在调节癌症的发展、生长和转移中起关键作用。生物信息学预测确定了 OC 中差异表达的 SRY-box 9 (SOX9) 和调节性 miRNA miR-139-5p。在这里，我们旨在评估外泌体 miR-139-5p 在卵巢癌 (OC) 细胞对顺式二氨二氯铂 (II) (DDP) 敏感性中的功能。使用逆转录定量聚合酶链反应和蛋白质印迹分析确定了 miR-139-5p 和 SOX9 在卵巢癌细胞 (SKOV3) 和 DDP 抗性细胞 (SKOV3/DDP) 中的表达模式。使用双荧光素酶报告基因检测验证了 miR-139-5p 和 SOX9 之间的关系。SKOV3/DDP 细胞系被开发并引入 miR-30a-5p 模拟物以分析 miR-30a-5p 对 DDP 抗性的影响。在外泌体和 OC 细胞的共培养系统以及荷瘤裸鼠中评估了外泌体 miR-30a-5p 对 SKOV3 细胞对 DDP 抗性的体外和体内影响。在 OC 中见证了 SOX9 的高表达和 miR-30-5p 的低表达。此外，miR-30-5p 是 SKOV3/DDP 细胞中下调的 miRNA，通过靶向 SOX9 增加细胞凋亡率并增强 SKOV3/DDP 细胞对 DDP 的敏感性。此外，在体外和体内，携带 miR-30a-5p 的外泌体被鉴定为使 SKOV3/DDP 细胞对 DDP 敏感。这些数据共同支持了一个重要结论，即抗 DDP OC 细胞衍生的外泌体 miR-30a-5p 增强了细胞对 DDP 的敏感性，