Effect of miR-29 on cisplatin sensitivity of ovarian cancer cells

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, ILIn clinical practice, the main dilemma to a successful ovarian cancer therapy is the development of drug resistance. The mounting evidence demonstrated that microRNAs (miRNAs) not only controlled cell proliferation, invasion and metastasis but also therapeutic resistance of ovarian cancer cell. Recently, we isolated CP70sps(CP70 side population spheres) from CP70 ovarian cancer cell line and proved that CP70sps exhibited more resistant to cisplatin than CP70. This phenomenon was correlated to other study which supported that side population of cancer cells was responsible for chemoresistance. In this study, we compared the expression of miRNAs between CP70sps and CP70 to investigate the role of miRNAs in cisplatin resistance of ovarian cancer cells. Our miRNA array and quantitative RT-PCR data showed that CP70sps expressed lower level of miR-29a/b/c family than CP70 cells and CP70sps4wks cells which were repopulation of CP70sps in attached condition. After knockdown of miR-29a/b/c family by miRNA inhibitors, reduction of miR-29a/b/c family enhanced cisplatin resistance of CP70 cells. However, there was no effect on cell cycle and proliferation rate in both CP70 cells and A2780, a parental cisplatin-sensitive cell line of CP70 cells. Downregulation of miR-29a/b/c family contributed cells to escape cisplatin-induced cell death through COL1A1 upregulation. Moreover, reduction of miR-29a/b/c increased phosphorylation of ERK1/2 and GSK3β to transduce survival signaling and reduced active form casepase-9 to avoid cell apoptosis. Furthermore, we found that either ectopic expression of miR-29 alone or combination of miR-29 with cisplatin treatment efficaciously reduced tumorigenicity of CP70 cells in immunodeficiency mice. Finally, we ascertained that the ovarian cancer patients with high expression of miR-29a had better overall survival rate. Taken together, our data demonstrated that the miR-29 family was a sensitizer for cisplatin treatment and might be associated with tumorigenecity of ovarian cancer cells.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1110. doi:1538-7445.AM2012-1110