Mi Lin, Chen Yaosheng, Zheng Xueli, Li Youlei, Zhang Qiangling, Mo Delin, Yang Gongshe
Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling, China.
College of Life Science, Sun Yat-Sen University, Guangzhou, China.
J Cell Biochem. 2015 Jul;116(7):1195-204. doi: 10.1002/jcb.25065.
MicroRNAs (miRNAs) participate in the regulation of adipogenesis. Identification of the full repertoire of miRNAs expressed in adipose tissue is likely to significantly improve our understanding of adipose tissue growth and development. Here, miR-139-5p was identified as an inhibitor of 3T3-L1 adipocyte differentiation with significantly down-regulating the expression levels of adipogenic marker genes PPAR γ (P < 0.01), aP2 (P < 0.01) and FAS (P < 0.01). Importantly, flow cytometry and EdU incorporation assay indicated that this inhibition was partly due to the dysfunction of clonal expansion. Furthermore, we firstly demonstrated that miR-139-5p blocked adipogenesis via directly targeted the 3' untranslated regions (UTRs) of Notch1 and IRS1 mRNAs, a key member of Notch signaling and IRS1/PI3K/Akt insulin signaling, respectively. In addition, the overexpression of Notch1 or IRS1 partially restored the suppressive effects miR-139-5p on differentiation of 3T3-L1 cells. To our knowledge, this was the first report that miR-139-5p functioned negatively by targeting Notch1 and IRS1 during 3T3-L1 adipogenesis, regulating the transition from clonal expansion to terminal differentiation.
微小RNA（miRNA）参与脂肪生成的调控。鉴定脂肪组织中表达的全部miRNA种类可能会显著增进我们对脂肪组织生长和发育的理解。在此，miR-139-5p被鉴定为3T3-L1脂肪细胞分化的抑制剂，它能显著下调脂肪生成标记基因PPARγ（P<0.01）、aP2（P<0.01）和FAS（P<0.01）的表达水平。重要的是，流式细胞术和EdU掺入试验表明，这种抑制作用部分归因于克隆扩增功能障碍。此外，我们首次证明miR-139-5p通过直接靶向Notch1和IRS1 mRNA的3'非翻译区（UTR）来阻断脂肪生成，Notch1是Notch信号通路的关键成员，IRS1是IRS1/PI3K/Akt胰岛素信号通路的关键成员。此外，Notch1或IRS1的过表达部分恢复了miR-139-5p对3T3-L1细胞分化的抑制作用。据我们所知，这是首次报道miR-139-5p在3T3-L1脂肪生成过程中通过靶向Notch1和IRS1发挥负向作用，调控从克隆扩增到终末分化的转变。
