title: miR-195a inhibits adipocyte differentiation by targeting the preadipogenic determinator Zfp423.
abstract: MicroRNAs (miRNAs) play essential roles in various cellular processes including proliferation and differentiation. In this study, we identified miRNA-195a (miR-195a) as a regulator of adipocyte differentiation. Differential expression of miR-195a in preadipocytes and adipocytes suggests its role in lipid accumulation and adipocyte differentiation. Forced expression of miR-195a mimics suppressed lipid accumulation and inhibited expression of adipocyte markers such as PPARγ and aP2 in 3T3-L1 and C3H10T1/2 cells. Conversely, downregulation of miR-195a by anti-miR-195a increased lipid accumulation and expression of adipocyte markers. Target prediction analysis suggested zinc finger protein 423 (Zfp423), a preadipogenic determinator, as a potential gene recognized by miR-195a. In line with this, mimicked expression of miR-195a reduced the expression of Zfp423, whereas anti-miR-195a increased its expression. Predicted targeting sequences in Zfp423 3'UTR, but not mutated sequences fused to luciferase, were regulated by miR-195a. Ectopic Zfp423 expression in 3T3-L1 cells increased lipid accumulation and expression of adipocyte markers, consistent with the observation that miR-195a targets Zfp423, resulting in suppressed adipocyte differentiation. In addition, miR-195a and Zfp423 were inversely correlated in obese fat tissues, raising the possibility of miRNA's role in obesity. Together, our data show that miR-195a is an anti-adipogenic regulator, which acts by targeting Zfp423, and further suggest the roles of miR-195a in obesity and metabolic diseases.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Ui Jeong
authors.initials: UJ
authors.lastname: Yun
authors.affiliation: Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: No-Joon
authors.initials: NJ
authors.lastname: Song
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, USA.|College of Life Science, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Dong Kwon
authors.initials: DK
authors.lastname: Yang
authors.affiliation: Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: So-Mi
authors.initials: SM
authors.lastname: Kwon
authors.affiliation: Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 406-772, Republic of Korea.
authors.forename: Kwangho
authors.initials: K
authors.lastname: Kim
authors.affiliation: New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 701-310, Republic of Korea.
authors.forename: Sunghwan
authors.initials: S
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Dong-Gyu
authors.initials: DG
authors.lastname: Jo
authors.affiliation: College of Life Science, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Woo Jin
authors.initials: WJ
authors.lastname: Park
authors.affiliation: Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Kye Won
authors.initials: KW
authors.lastname: Park
authors.affiliation: Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 406-772, Republic of Korea.
authors.forename: Hara
authors.initials: H
authors.lastname: Kang
mesh_terms: D020413:3' Untranslated Regions; D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D005786:Gene Expression Regulation; D050356:Lipid Metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; C484557:Ebfaz protein, mouse; C569389:MIRN195a microRNA, mouse; D035683:MicroRNAs; D014157:Transcription Factors
keywords: ADIPOCYTE DIFFERENTIATION; OBESITY; Zfp423; miR-195a