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. J. Cell. Biochem. 116: 2589–2597, 2015. © 2015 Wiley Periodicals, Inc.