MicroRNA MiR-214 Regulates Ovarian Cancer Cell Stemness by Targeting p53/Nanog

Abstract

Background: Ovarian cancer stem cells (OCSC) play a critical role in chemoresistance and relapse. Results: Expression of miR-214 induces, whereas knockdown of miR-214 decreases, OCSC and Nanog. MiR-214 targets p53, a repressor of Nanog. Conclusion: miR-214 targets p53 to induce OCSC and Nanog. Significance: MiR-214 is a target for OCSC. Previous studies have shown aberrant expression of miR-214 in human malignancy. Elevated miR-214 is associated with chemoresistance and metastasis. In this study, we identified miR-214 regulation of ovarian cancer stem cell (OCSC) properties by targeting p53/Nanog axis. Enforcing expression of miR-214 increases, whereas knockdown of miR-214 decreases, OCSC population and self-renewal as well as the Nanog level preferentially in wild-type p53 cell lines. Furthermore, we found that p53 is directly repressed by miR-214 and that miR-214 regulates Nanog through p53. Expression of p53 abrogated miR-214-induced OCSC properties. These data suggest the critical role of miR-214 in OCSC via regulation of the p53-Nanog axis and miR-214 as a therapeutic target for ovarian cancer.