Department of Molecular Oncology, University of South Florida, Tampa, Florida.
Cancer Epidemiology, University of South Florida, Tampa, Florida.
J Biol Chem. 2012 Oct 12;287(42):34970-34978. doi: 10.1074/jbc.M112.374611. Epub 2012 Aug 27.
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.
先前的研究表明，miR-214 在人类恶性肿瘤中表达异常。升高的 miR-214 与化疗耐药和转移有关。在这项研究中，我们通过靶向 p53/Nanog 轴鉴定了 miR-214 对卵巢癌细胞干细胞（OCSC）特性的调控。强制表达 miR-214 增加，而敲低 miR-214 减少，OCSC 群体和自我更新以及 Nanog 水平，特别是在野生型 p53 细胞系中。此外，我们发现 p53 被 miR-214 直接抑制，miR-214 通过 p53 调节 Nanog。p53 的表达消除了 miR-214 诱导的 OCSC 特性。这些数据表明，miR-214 通过调节 p53-Nanog 轴在 OCSC 中发挥关键作用，miR-214 是治疗卵巢癌的一个有潜力的靶点。
