MicroRNA-27 (miR-27) Targets Prohibitin and Impairs Adipocyte Differentiation and Mitochondria! Function in Human Adipose-derived Stem Cells

Background: Prohibitin is essential in adipocyte differentiation and mitochondrial functions, but the regulative mechanisms of prohibitin by microRNA remain unclear. Results: miR-27 negatively regulates adipogenesis by targeting prohibitin and impairing mitochondrial biogenesis, structure, and activity. Conclusion: miR-27 targets prohibitin and suppresses adipocyte differentiation. Significance: Manipulation of miR-27 may offer opportunities for the therapeutic modulation of adipogenesis in obesity. 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.