MicroRNA MiR-214 regulates ovarian cancer cell stemness by targeting p53/Nanog.
MicroRNA MiR-214 regulates ovarian cancer cell stemness by targeting p53/Nanog.
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DOI：
10.1074/jbc.a112.374611
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发表时间：
2012-10
期刊：
影响因子：
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通讯作者：
Cheng-Xiong Xu;Meng Xu;Lei Tan;Huan Yang;Jennifer Permuth‐Wey;P. Kruk;R. Wenham;S. Nicosia;J. Lancaster;T. Sellers;J. Cheng
中科院分区：
文献类型：
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作者：
Cheng-Xiong Xu;Meng Xu;Lei Tan;Huan Yang;Jennifer Permuth‐Wey;P. Kruk;R. Wenham;S. Nicosia;J. Lancaster;T. Sellers;J. Cheng
先前的研究表明 miR-214 在人类恶性肿瘤中存在异常表达。 miR-214 升高与化疗耐药和转移相关。在这项研究中，我们通过靶向 p53/Nanog 轴确定了 miR-214 对卵巢癌干细胞 (OCSC) 特性的调节。在野生型 p53 细胞系中，加强 miR-214 的表达会增加，而 miR-214 的敲除会减少，OCSC 数量和自我更新以及 Nanog 水平优先增加。此外，我们发现p53直接被miR-214抑制，并且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，并且 miR-214 作为卵巢癌的治疗靶点。
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.