miR-34c Targets MET to Improve the Anti-Tumor Effect of Cisplatin on Ovarian Cancer

• Main Authors: Yang S, Li Z, Luo R
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-04-01
• Series: OncoTargets and Therapy
• Subjects: ovarian cancer; mir-34c; cisplatin; met; bad
• Online Access: https://www.dovepress.com/mir-34c-targets-met-to-improve-the-anti-tumor-effect-of-cisplatin-on-o-peer-reviewed-article-OTT

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 [e-mail]: 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