title: MicroRNA hsa-miR-138 inhibits adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells through adenovirus EID-1.
abstract: A better understanding of the molecular mechanisms underlying the differentiation of human adipose tissue-derived mesenchymal stem cells (hAD-MSCs) could provide new insights into the pathogenesis of a number of diseases, such as obesity and diabetes, and broaden the spectrum of potential hAD-MSCs-based cell therapy. In this study, we reported that a human microRNA, hsa-miR-138, could inhibit the adipogenic differentiation of hAD-MSCs. Our results showed that miR-138 was significantly down-regulated during adipogenic differentiation. Overexpression of miR-138 in hAD-MSCs could effectively reduce lipid droplets accumulation, inhibit expression of key adipogenic transcription factors cytidine-cytidine-adenosine-adenosine-thymidine (CCAAT) enhancer binding protein alpha and peroxisome proliferator-activated receptor gamma 2 as well as several other adipogenic marker genes, such as fatty acid binding protein 4 and lipoprotein lipase. Further studies showed that the expression of adenovirus early region 1-A-like inhibitor of differentiation 1 (EID-1), a nuclear receptor coregulator, was inversely correlated with that of miR-138 when hAD-MSCs were differentiated into adipocytes. Knockdown of EID-1 by RNA interference inhibited adipocyte differentiation of hAD-MSCs. In addition, luciferase reporter assays demonstrated that miR-138 directly targeted the 3' untranslated region of EID-1, implying that the negative role of miR-138 in the adipocyte differentiation of hAD-MSCs is at least partially mediated via repressing EID-1. Taken together, this study shows that miR-138 plays a negative role in adipogenic differentiation and sheds light on the role of miRNAs during differentiation of hAD-MSCs toward adipocytes.
authors.affiliation: Center of Excellence in Tissue Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Institute of Basic Medical Sciences and School of Basic Medicine, Beijing, PR China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Yang
authors.forename: Chunjing
authors.initials: C
authors.lastname: Bian
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.forename: Shan
authors.initials: S
authors.lastname: Huang
authors.forename: Shihua
authors.initials: S
authors.lastname: Wang
authors.forename: Lianming
authors.initials: L
authors.lastname: Liao
authors.forename: Robert Chunhua
authors.initials: RC
authors.lastname: Zhao
mesh_terms: D020413:3' Untranslated Regions; D000256:Adenoviridae / Q000235:genetics; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology*; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D055785:Gene Knockdown Techniques; D017930:Genes, Reporter; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D035683:MicroRNAs / Q000096:biosynthesis*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D018797:Cell Cycle Proteins; C416925:EID1 protein, human; C546110:MIRN138 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D012097:Repressor Proteins