miR-17-92 cluster accelerates adipocyte differentiation by negatively regulating tumor-suppressor Rb2/p130.
Adipogenesis involves cell proliferation and differentiation, both of which have been shown to be regulated by micro (mi)RNA. During mouse preadipocyte 3T3L1 cell differentiation, we found that miR-17-92, a miRNA cluster that promotes cell proliferation in various cancers, was significantly up-regulated at the clonal expansion stage of adipocyte differentiation. Stable transfection of 3T3L1 cells with miR-17-92 resulted in accelerated differentiation and increased triglyceride accumulation after hormonal stimulation. By using a luciferase reporter assay, we demonstrated that miR-17-92 directly targeted the 3' UTR region of Rb2/p130, accounting for subsequently reduced Rb2/p130 mRNA and protein quantities at the stage of clonal expansion. siRNA-mediated knock-down of Rb2/p130 at the same stage of clonal expansion recapitulated the phenotype of overexpression of miR-17-92 in the stably transfected 3T3L1 cells. These data indicate that miR-17-92 promotes adipocyte differentiation by targeting and negatively regulating Rb2/p130.
Wang
Qiang
Q
Department of Medicine, Biological Sciences Division, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
Li
Yan Chun
YC
Wang
Jinhua
J
Kong
Juan
J
Qi
Yuchen
Y
Quigg
Richard J
RJ
Li
Xinmin
X
D020413:3' Untranslated Regions / Q000235:genetics / Q000378:metabolism; D041721:3T3-L1 Cells; D017667:Adipocytes / Q000502:physiology*; D000818:Animals; D001391:Azo Compounds; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D017931:DNA Primers; D005786:Gene Expression Regulation; D008156:Luciferases; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000502:physiology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D050717:Retinoblastoma-Like Protein p130 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020413:3' Untranslated Regions; D001391:Azo Compounds; D017931:DNA Primers; D035683:MicroRNAs; D034741:RNA, Small Interfering; C493838:Rbl2 protein, mouse; D050717:Retinoblastoma-Like Protein p130; D008156:Luciferases; C011049:oil red O