title: MicroRNA-27 (miR-27) targets prohibitin and impairs adipocyte differentiation and mitochondrial function in human adipose-derived stem cells.
abstract: Prohibitin (PHB) has been reported to play a crucial role in adipocyte differentiation and mitochondrial function. However, the regulative mechanism of PHB during adipogenesis remains unclear. In this study, we determined that the levels of both microRNA (miR)-27a and miR-27b were down-regulated following adipogenic induction of human adipose-derived stem cells, whereas the mRNA level of PHB was up-regulated. Overexpression of miR-27a or miR-27b inhibited PHB expression and adipocyte differentiation. Using PHB 3'-UTR luciferase reporter assay, we observed that miR-27a and miR-27b directly targeted PHB in human adipose-derived stem cells. A compensation of PHB partially restored the adipogenesis inhibited by miR-27. Moreover, we demonstrated the novel finding that ectopic expression of miR-27a or miR-27b impaired mitochondrial biogenesis, structure integrity, and complex I activity accompanied by excessive reactive oxygen species production. Our data suggest that miR-27 is an anti-adipogenic microRNA partly by targeting PHB and impairing mitochondrial function. Pharmacological modulation of miR-27 function may provide a new therapeutic strategy for the treatment of obesity.
authors.affiliation: From the Cardiovascular Research Institute.
authors.forename: Ting
authors.initials: T
authors.lastname: Kang
authors.forename: Wan
authors.initials: W
authors.lastname: Lu
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Leonard
authors.initials: L
authors.lastname: Anderson
authors.forename: Methode
authors.initials: M
authors.lastname: Bacanamwo
authors.forename: Winston
authors.initials: W
authors.lastname: Thompson
authors.forename: Y Eugene
authors.initials: YE
authors.lastname: Chen
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D015536:Down-Regulation; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D009765:Obesity / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000091402:Prohibitins; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells; D015854:Up-Regulation
chemical_list: C531388:MIRN27 microRNA, human; D035683:MicroRNAs; C000717328:PHB protein, human; D000091402:Prohibitins; D016601:RNA-Binding Proteins; D017382:Reactive Oxygen Species; D012097:Repressor Proteins
keywords: Adipogenesis; Cell Differentiation; MicroRNA; Mitochondria; Prohibitin; Stem Cells; miR-27