title: p53-facilitated miR-199a-3p regulates somatic cell reprogramming.
abstract: 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.
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, People's Republic of China.
authors.forename: Jiaxu
authors.initials: J
authors.lastname: Wang
authors.forename: Qianqian
authors.initials: Q
authors.lastname: He
authors.forename: Chuanchun
authors.initials: C
authors.lastname: Han
authors.forename: Hao
authors.initials: H
authors.lastname: Gu
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.forename: Qun
authors.initials: Q
authors.lastname: Li
authors.forename: Yide
authors.initials: Y
authors.lastname: Mei
authors.forename: Mian
authors.initials: M
authors.lastname: Wu
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000235:genetics / Q000502:physiology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53