OncoTargets and Therapy (Apr 2020)
miR-34c Targets MET to Improve the Anti-Tumor Effect of Cisplatin on Ovarian Cancer
Abstract
Shiying Yang,1 Zhen Li,2 Rui Luo3 1Department of Gynecology and Obstetrics, Rizhao People’s Hospital, Rizhao City 276800, Shandong Province, People’s Republic of China; 2Reproductive Medicine Center, Qingdao Women and Children Hospital, Qingdao City 266011, Shandong Province, People’s Republic of China; 3Department of Gynecology, Linyi People’s Hospital, Linyi City 276000, Shandong Province, People’s Republic of ChinaCorrespondence: Rui Luo Email [email protected]: Cisplatin is a commonly used drug for the treatment of various types of malignant cancers, including ovarian cancer. However, resistance to cisplatin is still a considerable obstacle to achieve a satisfactory therapeutic effect. The purpose of this study is to develop a strategy to sensitize ovarian cancer cells to cisplatin-induced cytotoxicity.Methods: miR-34c levels in ovarian cancer tissues and cell lines were tested by qRT-PCR analysis. In vitro assays, the effect of miR-34c on cisplatin was evaluated by using MTT. Expression of MET and phosphorylation of PI3K and AKT were tested by Western blot assays. Conjugation with Bad and Bcl-xl was evaluated through immunoprecipitation. Flow cytometry analysis was performed to measure the apoptotic rate of ovarian cancer cells.Results: Downregulation of miR-34c was observed in ovarian cancer tissues and cell lines. However, miR-34c overexpression was found to sensitize ovarian cancer cells to cisplatin treatment in vitro and in vivo. Mechanically, we found that miR-34c targeted the MET gene, thereby inhibiting the phosphorylation of PI3K and AKT to activate Bad. As a result, miR-34c reduced resistance of ovarian cancer cells to cisplatin-induced apoptosis.Conclusion: miR-34c/MET axis promotes cisplatin-induced cytotoxicity against ovarian cancer by targeting the MET/PI3K/AKT/Bad pathway.Keywords: ovarian cancer, miR-34c, cisplatin, MET, Bad
