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

Abstract

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.

Chronically dysregulated NOTCH1 interactome in the dentate gyrus after traumatic brain injury

“…In parallel, levels of Notch1 mRNA were elevated and the protein level of activated NOTCH1 was increased. Our data are consistent with those of previous experimental studies showing regulation of Notch1 mRNA by miR-139-5p [42–44, 60]. Moreover, both miR-139-5p [43] and the 3’ untranslated region of the Notch1 [41] appear well-conserved among mammals, further emphasizing the true regulative potential of miR-139-5p on Notch1 mRNA.…”

“…We then confirmed the expression of Notch1 and its regulator, miR-139-5p [42–44]. Quantitative RT-PCR confirmed the upregulation of Notch1 (p<0.05, Fig 4C).…”

Downregulation of miR-139-5p contributes to the antiapoptotic effect of liraglutide on the diabetic rat pancreas and INS-1 cells by targeting IRS1

“…One is that dipeptidyl peptidase-4 inhibition improves β-cell function in db/db mice, but not in any of the IRS1-deficient mouse strains [28]. The other is that MicroRNA-139-5p suppresses 3T3-L1 preadipocyte differentiation through Notch and IRS1/PI3K/Akt insulin signaling pathways[29]. Whether inhibition of IRS1 can promote the effects of miR-139-5p on apoptosis of INS-1 cells needs to be further investigated.…”

Effect of microRNA-208a on mitochondrial apoptosis of cardiomyocytes of neonatal rats

“…The microRNAs (miRNA) is a kind of small non-coding singlestrand RNA with the length of about 18-25 nucleotides [8,9] . The first miRNA (lin-4) was discovered by Lee et al in Caenorhabditis elegans using the method genetic analysis in 1993 [10,11].…”