title: 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.
authors.affiliation: Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Mi
authors.affiliation: College of Life Science, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Yaosheng
authors.initials: Y
authors.lastname: Chen
authors.affiliation: College of forestry, Northwest A&F University, Yangling, China.
authors.forename: Xueli
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling, China.
authors.forename: Youlei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling, China.
authors.forename: Qiangling
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: College of Life Science, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Delin
authors.initials: D
authors.lastname: Mo
authors.forename: Gongshe
authors.initials: G
authors.lastname: Yang
mesh_terms: D016475:3T3 Cells; D050156:Adipogenesis; D000818:Animals; D015536:Down-Regulation; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; C546202:MIRN139 microRNA, mouse; D035683:MicroRNAs; D047495:PPAR gamma; D051880:Receptors, Notch
keywords: 3T3-L1; ADIPOCYTE DIFFERENTIATION; IRS1/PI3K/Akt INSULIN SIGNALING; NOTCH SIGNALING; miR-139-5p