Exosomal transfer of miR-548aq-3p confers cisplatin resistance via MED12 downregulation in epithelial ovarian cancer.

The RNA polymerase II mediator complex subunit 12 (MED12) is an important factor for chemotherapy sensitivity. We explored the roles of exosomal transfer of carcinogenic microRNAs (miRNAs) in MED12 regulation and cisplatin resistance of ovarian cancer cells. In this study, the correlation between MED12 expression and cisplatin resistance was analyzed in ovarian cancer cells. The molecular regulation of MED12 by exosomal miR-548aq-3p was investigated by bioinformatics analysis and luciferase reporter assays. Further clinical significance of miR-548aq was assessed with TCGA data. We identified decreased MED12 expression in cisplatin-resistance of ovarian cancer cells. More importantly, coculture with cisplatin-resistant cells attenuated cisplatin sensitivity of parental ovarian cancer cells, as well as reduced MED12 expression to a large extent. Further bioinformatic analysis identified that exosomal miR-548aq-3p was correlated with MED12 transcriptional regulation in ovarian cancer cells. Luciferase reporter assays demonstrated that miR-548aq-3p down-regulated MED12 expression. miR-548aq-3p overexpression enhanced cell survival and proliferation of ovarian cancer cells with cisplatin treatment, while miR-548aq-3p inhibition induced cell apoptosis of cisplatin-resistant cells. Further clinical analysis indicated that miR-548aq was correlated with lower MED12 expression. More importantly, miR-548aq expression was a detrimental factor in the disease progression of ovarian cancer patients. In conclusion, we found that miR-548aq-3p contributed to cisplatin chemotherapy resistance of ovarian cancer cells through MED12 downregulation. Our study supported miR-548aq-3p as a promising therapeutic target for improving chemotherapy sensitivity of ovarian cancer.