接触抑制阶段miR-29a/b/c表达下调通过靶向DNMT3A促进3T3-L1脂肪生成。
Downregulated miR-29a/b/c during Contact Inhibition Stage Promote 3T3-L1 Adipogenesis by Targeting DNMT3A.
作者信息
Zhu Yingjie, Zheng Guangyong, Wang Huichao, Jia Yudong, Zhang Ying, Tang Yanfeng, Li Wenlong, Fan Yanan, Zhang Xiaodong, Liu Youwen, Liu Sanhong
机构信息
Henan Provincial Luoyang Orthopedic-Traumatological Hospital (Henan Provincial Orthopedic Hospital), Luoyang, Henan, China.
CAS-MPG Partner Institute for Computational Biology, Chinese Academy of Sciences, Shanghai, China.
出版信息
PLoS One. 2017 Jan 23;12(1):e0170636. doi: 10.1371/journal.pone.0170636. eCollection 2017.
Differentiation of 3T3-L1 cells into adipocytes involves a highly-orchestrated series of events including contact inhibition (CI), clonal expansion, growth arrest, and terminal differentiation. Recent study demonstrated that 3T3-L1 preadipocytes will not be differentiated into mature adipocytes without CI stage, which indicated that CI stage plays an important role during 3T3-L1 adipogenesis. However, the molecular mechanism is not yet fully understood. In the present study, we found that the expression level of miR-29a/b/c was decreased and the expression of DNMT3A was up-regulated during CI stage, respectively. Furthermore, overexpression of miR-29a/b/c during CI stage inhibits adipogenesis significantly but not at other stages. In addition, miR-29a/b/c repressed DNMT3A expression by directly targeting its 3' untranslated region (3' UTR). Our data reveal a novel mechanism of miR-29a/b/c in the regulation of adipogenesis.
3T3-L1细胞向脂肪细胞的分化涉及一系列高度协调的事件，包括接触抑制（CI）、克隆扩增、生长停滞和终末分化。最近的研究表明，3T3-L1前脂肪细胞如果没有CI阶段就不会分化为成熟脂肪细胞，这表明CI阶段在3T3-L1脂肪生成过程中起着重要作用。然而，其分子机制尚未完全阐明。在本研究中，我们发现miR-29a/b/c的表达水平在CI阶段分别降低，而DNMT3A的表达上调。此外，在CI阶段过表达miR-29a/b/c可显著抑制脂肪生成，但在其他阶段则不然。另外，miR-29a/b/c通过直接靶向DNMT3A的3'非翻译区（3'UTR）来抑制其表达。我们的数据揭示了miR-29a/b/c调控脂肪生成的一种新机制。
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