MicroRNA-199a Targets the Fatty Acid Transport Protein 1 Gene and Inhibits the Adipogenic Trans-Differentiation of C2C12 Myoblasts

Abstract

Background/Aims: Muscle cells are able to trans-differentiate into adipocytes with adipogenesis induction. MicroRNAs (miRNAs), a class of small non-coding RNAs, widely participate in the regulation of growth and development of cells. However, the expression and regulatory role of miRNAs in the trans-differentiation of muscle cell are largely unknown. Methods: C2C12 myoblasts were inducted to adipogenesis trans-differentiation and microarrays were used to assay the changes of expression profile of miRNAs. MiR-199a, a miRNA showed significant change in the trans-differentiation, was selected for the subsequent function study via over- expression and knock down. Results: Dozens of miRNAs showed different changes followed the adipogenesis trans-differentiation of C2C12 cells. In which, miR-199a was decreased in the adipogenic cells and miR-199a over-expression inhibited the trans-differentiation and decreased lipid accumulation in the cells. Moreover, Fatty acid transport protein 1 (Fatp1), a major regulator of trans-membrane transportation and the oxidative metabolism of free fatty acids, was showed to be a target of miR-199a by computational and luciferase reporter assays. Additionally, Fatp1 knock-down by small interfering RNA had similar inhibitory effects on the trans-differentiation in C2C12 cells. Conclusion: Our study reveals an important role for miR-199a in the regulation of adipogenic trans-differentiation in muscle cells via suppression of Fatp1 gene.

Keywords

• MiR-199a
• Fatp1
• C2C12 cells
• Adipogenesis
• Trans-differentiation