MiR-25 suppresses 3T3-L1 adipogenesis by directly targeting KLF4 and C/EBPα.
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.
School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, P.R. China.|Croucher Laboratory for Human Genomics, The Chinese University of Hong Kong, Shatin, Hong Kong, P.R. China.
Wei-Cheng
WC
Liang
School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, P.R. China.
Yan
Y
Wang
Key Laboratory of Gene Engineering of Ministry of Education and State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, P.R. China.
Pu-Ping
PP
Liang
School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, P.R. China.
Xu-Qing
XQ
Pan
Guangzhou Institute of Advanced Technology, Chinese Academy of Sciences, Guangzhou, P.R. China.
Wei-Ming
WM
Fu
School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, P.R. China.|Croucher Laboratory for Human Genomics, The Chinese University of Hong Kong, Shatin, Hong Kong, P.R. China.
Venus Sai-Ying
VS
Yeung
Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, P.R. China.
Ying-Fei
YF
Lu
School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, P.R. China.
David Chi-Cheong
DC
Wan
School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, P.R. China.|Croucher Laboratory for Human Genomics, The Chinese University of Hong Kong, Shatin, Hong Kong, P.R. China.|The Hong Kong Bioinformatics Centre, The Chinese University of Hong Kong, Shatin, Hong Kong, P.R. China.
Stephen Kwok-Wing
SK
Tsui
School of Life Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, P.R. China.
Suk-Ying
SY
Tsang
Key Laboratory of Gene Engineering of Ministry of Education and State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, P.R. China.
Wen-Bin
WB
Ma
Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, P.R. China.
Jin-Fang
JF
Zhang
School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, P.R. China.|Croucher Laboratory for Human Genomics, The Chinese University of Hong Kong, Shatin, Hong Kong, P.R. China.
Mary Miu-Yee
MM
Waye
D041721:3T3-L1 Cells; D050156:Adipogenesis; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D011401:Promoter Regions, Genetic
D022762:CCAAT-Enhancer-Binding Proteins; C530718:CEBPA protein, mouse; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C558895:MIRN25 microRNA, mouse; D035683:MicroRNAs
3T3-L1; ADIPOGENESIS; MicroRNA; miR-25