MiR-25 Suppresses 3T3-L1 Adipogenesis by Directly Targeting KLF4 and C/EBPα

• Published in: Journal of cellular biochemistry Vol. 116; no. 11; pp. 2658 - 2666
• Main Authors: Liang, Wei-Cheng, Wang, Yan, Liang, Pu-Ping, Pan, Xu-Qing, Fu, Wei-Ming, Yeung, Venus Sai-Ying, Lu, Ying-Fei, Wan, David Chi-Cheong, Tsui, Stephen Kwok-Wing, Tsang, Suk-Ying, Ma, Wen-Bin, Zhang, Jin-Fang, Waye, Mary Miu-Yee
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.11.2015; Wiley Subscription Services, Inc
• Subjects: 3T3-L1; 3T3-L1 Cells; Adipocytes; ADIPOGENESIS; Animals; CCAAT-Enhancer-Binding Proteins - genetics; Cell cycle; Cell Differentiation; Cell fate; Cell proliferation; Differentiation (biology); Ectopic expression; Embryogenesis; Embryonic growth stage; Gene Expression Regulation; Gene regulation; Homeostasis; Kinases; KLF4 protein; Kruppel-Like Transcription Factors - genetics; Mice; MicroRNA; MicroRNAs - metabolism; miR-25; miRNA; Molecular modelling; Peroxisome proliferator-activated receptors; Promoter Regions, Genetic; Transcription factors; MicroRNA; ADIPOGENESIS; 3T3-L1; miR-25
• ISSN: 0730-2312; 1097-4644; 1097-4644
• DOI: 10.1002/jcb.25214

ABSTRACT In the past decade, miRNA emerges as a vital player in orchestrating gene regulation and maintaining cellular homeostasis. It is well documented that miRNA influences a variety of biological events, including embryogenesis, cell fate decision, and cellular differentiation. Adipogenesis is an organized process of cellular differentiation by which pre‐adipocytes differentiate towards mature adipocytes. It has been shown that adipogenesis is tightly modulated by a number of transcription factors such as PPARγ, KLF4, and C/EBPα. However, the molecular mechanisms underlying the missing link between miRNA and adipogenesis‐related transcription factors remain elusive. In this study, we unveiled that miR‐25, a member of miR‐106b‐25 cluster, was remarkably downregulated during 3T3‐L1 adipogenesis. Restored expression of miR‐25 significantly impaired 3T3‐L1 adipogenesis and downregulated the expression of serial adipogenesis‐related genes. Further experiments presented that ectopic expression of miR‐25 did not affect cell proliferation and cell cycle progression. Finally, KLF4 and C/EBPα, two key regulators of adipocyte differentiation, were experimentally identified as bona fide targets for miR‐25. These data indicate that miR‐25 is a novel negative regulator of adipocyte differentiation and it suppressed 3T3‐L1 adipogenesis by targeting KLF4 and C/EBPα, which provides novel insights into the molecular mechanism of miRNA‐mediated cellular differentiation. J. Cell. Biochem. 116: 2658–2666, 2015. © 2015 Wiley Periodicals, Inc.