A Novel Regulatory Circuit "C/EBPα/miR-20a-5p/TOB2" Regulates Adipogenesis and Lipogenesis.
C/EBPα
TOB2
adipocyte differentiation
lipogenesis
microRNA
Journal
Frontiers in endocrinology
ISSN: 1664-2392
Titre abrégé: Front Endocrinol (Lausanne)
Pays: Switzerland
ID NLM: 101555782
Informations de publication
Date de publication:
2019
2019
Historique:
received:
01
10
2019
accepted:
05
12
2019
entrez:
24
1
2020
pubmed:
24
1
2020
medline:
24
1
2020
Statut:
epublish
Résumé
Recent studies have identified growing importance of microRNAs as key regulators of adipocyte differentiation. We have previously reported that miR-20a-5p is able to induce adipogenesis of established adipogenic cell lines and bone marrow derived mesenchymal stem cells (BMSCs). However, the molecular mechanisms by which miR-20a-5p controls adipogenesis and by which miR-20a-5p expression is regulated need to be further explored. In the current study we found that miR-20a-5p expression was induced during adipocyte differentiation from preadipocyte 3T3-L1 and was increased in epididymal white adipose tissue from either ob/ob mice or high fat diet-induced obese mice. Functional studies identified miR-20a-5p as a positive regulator of adipocyte differentiation and lipogenesis in 3T3-L1 by using either synthetic mimics to supplement miR-20a-5p, or using synthetic inhibitor or sponge lentivirus to inactivate endogenous miR-20a-5p. Luciferase activity assay revealed that TOB2 is a novel target of miR-20a-5p and functional experiment demonstrated its negative regulatory role in adipocyte differentiation. Moreover, Tob2 overexpression significantly attenuated adipocyte formation induced by miR-20a-5p supplementation. In-depth investigation of mechanisms that govern miR-20a-5p expression clarified that C/EBPα transcriptionally activated miR-20a-5p expression via binding to the promoter of miR-20a-5p. Taken together, we conclude that a novel C/EBPα/miR-20a-5p/TOB2 circuit exists and regulates adipogenesis and lipogenesis.
Identifiants
pubmed: 31969862
doi: 10.3389/fendo.2019.00894
pmc: PMC6960138
doi:
Types de publication
Journal Article
Langues
eng
Pagination
894Informations de copyright
Copyright © 2020 Zhou, Yang, Wang, Li, Li, Zhu, Li, Li and Wang.
Références
Sci Rep. 2015 May 22;5:9930
pubmed: 26001136
J Endocrinol. 2009 May;201(2):263-74
pubmed: 19218285
Biomed Pharmacother. 2018 Jul;103:1482-1489
pubmed: 29864933
Acta Physiol (Oxf). 2017 Feb;219(2):346-361
pubmed: 27009502
J Clin Endocrinol Metab. 2004 Jun;89(6):2595-600
pubmed: 15181029
Curr Atheroscler Rep. 2014 Oct;16(10):441
pubmed: 25092577
FEBS Lett. 2014 Jan 31;588(3):429-35
pubmed: 24333578
FASEB J. 2017 May;31(5):1939-1952
pubmed: 28122918
Biochem Biophys Res Commun. 2008 Nov 28;376(4):728-32
pubmed: 18809385
Clin Exp Pharmacol Physiol. 2011 Apr;38(4):239-46
pubmed: 21291493
Cell Rep. 2018 Feb 20;22(8):2133-2145
pubmed: 29466739
Exp Biol Med (Maywood). 2001 Dec;226(11):997-1002
pubmed: 11743135
Mol Cell Biol. 2012 Dec;32(24):5067-77
pubmed: 23071089
J Mol Endocrinol. 2014 Jun;52(3):311-20
pubmed: 24850830
Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12532-7
pubmed: 11606718
Mol Cancer. 2018 Jul 12;17(1):98
pubmed: 30001707
Cell. 1994 Dec 30;79(7):1147-56
pubmed: 8001151
J Biol Chem. 2013 May 17;288(20):14264-75
pubmed: 23564456
J Mol Endocrinol. 2018 Apr;60(3):225-237
pubmed: 29348304
Int J Obes (Lond). 2017 May;41(5):729-738
pubmed: 28163317
Int J Obes (Lond). 2015 Aug;39(8):1282-91
pubmed: 25817070
Mol Cell. 1999 Oct;4(4):597-609
pubmed: 10549291
Cell. 2004 Jan 23;116(2):281-97
pubmed: 14744438
Nat Med. 2004 Apr;10(4):355-61
pubmed: 15057233
Cell Signal. 2014 Nov;26(11):2583-9
pubmed: 25038456
Nature. 2000 Apr 6;404(6778):635-43
pubmed: 10766250
FEBS Lett. 2008 Apr 16;582(9):1313-8
pubmed: 18358842