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

Autor: Venus S.Y. Yeung, Jinfang Zhang, Yan Wang, Wei-Cheng Liang, Ying Fei Lu, David Chi Cheong Wan, Mary M.Y. Waye, Xu Qing Pan, Wen Bin Ma, Pu Ping Liang, Weiming Fu, Stephen Kwok-Wing Tsui, Suk Ying Tsang
Rok vydání: 2015
Předmět:
Zdroj: Journal of Cellular Biochemistry. 116:2658-2666
ISSN: 1097-4644
0730-2312
DOI: 10.1002/jcb.25214
Popis: 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.
Databáze: OpenAIRE
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