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

Wei Cheng Liang, Yan Wang, Pu Ping Liang, Xu Qing Pan, Wei Ming Fu, Venus Sai Ying Yeung, Ying Fei Lu, David Chi Cheong Wan, Stephen Kwok Wing Tsui, Suk Ying Tsang, Wen Bin Ma, Jin Fang Zhang, Mary Miu Yee Waye

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2658-2666
Number of pages9
JournalJournal of Cellular Biochemistry
Volume116
Issue number11
DOIs
StatePublished - Nov 1 2015

Bibliographical note

Publisher Copyright:
© 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Keywords

  • 3T3-L1
  • ADIPOGENESIS
  • MicroRNA
  • miR-25

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