p53‐Facilitated miR‐199a‐3p Regulates Somatic Cell Reprogramming
p53‐Facilitated miR‐199a‐3p Regulates Somatic Cell Reprogramming
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DOI：
10.1002/stem.1121
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发表时间：
2012-07
期刊：
影响因子：
5.2
通讯作者：
Jiaxu Wang;Qianqian He;Chuanchun Han;Hao Gu;Lei Jin;Qun Li;Yide Mei;Mian Wu
中科院分区：
文献类型：
--
作者：
Jiaxu Wang;Qianqian He;Chuanchun Han;Hao Gu;Lei Jin;Qun Li;Yide Mei;Mian Wu
体细胞可以通过特定转录因子的异位表达重编程为诱导多能干细胞（iPSC）。然而，这一过程的效率极低。尽管最近研究表明p53的失活可以极大地提高重编程效率，但其潜在的分子机制在很大程度上仍然未知。在这里，我们报告了miR-199 a-3 p在转录后水平被p53上调。miR-199 a-3 p的诱导显著降低了重编程效率，而miR-199 a-3 p的抑制则大大增强了重编程效率。相反，miR-199 a-3 p抑制导致细胞增殖显著增加。此外，p53敲低细胞重编程的增强几乎完全被miR-199 a-3 p的替代所逆转。此外，miR-199 a-3 p抑制部分挽救了p53受损的iPS生成。这些发现表明miR-199 a-3 p是一种新的p53靶点，可负调控体细胞重编程。干细胞2012;30：1405-1413
Somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) by ectopic expression of defined transcriptional factors. The efficiency of this process, however, is extremely low. Although inactivation of p53 has been recently shown to greatly enhance reprogramming efficiency, the underlying molecular mechanisms still remain largely unknown. Here, we report that miR‐199a‐3p is upregulated by p53 at the post‐transcriptional level. Induction of miR‐199a‐3p significantly decreases reprogramming efficiency, whereas miR‐199a‐3p inhibition greatly enhances it. Mechanistically, miR‐199a‐3p overexpression inhibits cell proliferation by imposing G1 cell cycle arrest. Conversely, miR‐199a‐3p inhibition results in a pronounced increase in cell proliferation. Furthermore, the enhancement in reprogramming of p53 knockdown cells is almost completely reversed with replacement of miR‐199a‐3p. Also, miR‐199a‐3p inhibition partially rescues iPS generation impaired by p53. These findings suggest miR‐199a‐3p as a novel p53 target that negatively regulates somatic cell reprogramming. Stem Cells2012;30:1405–1413