MicroRNA-139-5p Suppresses 3T3-L1 Preadipocyte Differentiation Through Notch and IRS1/PI3K/Akt Insulin Signaling Pathways.

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.