title: miR-27 impairs the adipogenic lineage commitment via targeting lysyl oxidase.
abstract: OBJECTIVE
  The recruitment and commitment of mesenchymal stem cells and their terminal differentiation into adipocytes are the main pathways for increasing adipocyte cell numbers during obesity. Our previous studies have shown that lysyl oxidase (Lox) is upregulated and functions as an essential factor during bone morphogenetic protein 4 (BMP4) -induced C3H10T1/2 cell adipocytic lineage commitment. However, the mechanism of Lox regulation during adipogenic lineage commitment has remained largely unestablished.
  
  
  METHODS
  Samples of adipose tissue from humans with different BMI and C57BL/6 mice with a high-fat diet were used to compare microRNA-27 (miR-27) expression level associated with obesity. Taqman assays were used for miR-27 expression detection and Oil Red O staining for adipogenesis analysis.
  
  
  RESULTS
  A negative correlation was identified between Lox expression level and miR-27 expression in both BMP4-treated C3H10T1/2 cells and human subcutaneous adipose tissues. A Lox 3' UTR luciferase reporter assay showed that miR-27 directly targeted Lox. Furthermore, overexpression of miR-27 impaired BMP4-induced upregulation of Lox and adipocytic commitment, which could be rescued by overexpression of mature Lox. Conversely, miR-27 inhibition by specific inhibitors increased Lox expression and adipocytic commitment.
  
  
  CONCLUSIONS
  Taken together, these results suggest a novel role for miR-27 in repressing adipogenic lineage commitment by targeting Lox.
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Shanghai, People's Republic of China.|Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, People's Republic of China.
authors.forename: Su-Zhen
authors.initials: SZ
authors.lastname: Chen
authors.affiliation: Institute of Stem Cell Research and Regenerative Medicine, Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
authors.forename: Xu
authors.initials: X
authors.lastname: Xu
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Shanghai, People's Republic of China.|Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, People's Republic of China.
authors.forename: Liu-Fang
authors.initials: LF
authors.lastname: Ning
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Shanghai, People's Republic of China.|Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, People's Republic of China.
authors.forename: Wen-Yan
authors.initials: WY
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Shanghai, People's Republic of China.|Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, People's Republic of China.
authors.forename: Chun
authors.initials: C
authors.lastname: Xing
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Shanghai, People's Republic of China.|Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, People's Republic of China.|Institute of Stem Cell Research and Regenerative Medicine, Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
authors.forename: Qi-Qun
authors.initials: QQ
authors.lastname: Tang
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Shanghai, People's Republic of China.|Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, People's Republic of China.|Institute of Stem Cell Research and Regenerative Medicine, Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Huang
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics*; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D015992:Body Mass Index; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics*; D059305:Diet, High-Fat / Q000009:adverse effects; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D009765:Obesity / Q000201:enzymology / Q000209:etiology / Q000235:genetics; D008249:Protein-Lysine 6-Oxidase / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D055415:Bone Morphogenetic Protein 4; C531388:MIRN27 microRNA, human; D035683:MicroRNAs; C540674:Mirn27 microRNA, mouse; D008249:Protein-Lysine 6-Oxidase