MicroRNA-106b induces mitochondrial dysfunction and insulin resistance in C2C12 myotubes by targeting mitofusin-2.

Mol Cell Endocrinol 2013 Dec 14;381(1-2):230-40. Epub 2013 Aug 14.

Department of Pediatrics, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, People's Republic of China.

MicroRNA-106b (miR-106b) is reported to correlate closely with skeletal muscle insulin resistance and type 2 diabetes. The aim of this study was to identify an mRNA targeted by miR-106b which regulates skeletal muscle insulin sensitivity. MiR-106b was found to target the 3' untranslated region (3' UTR) of mitofusin-2 (Mfn2) through miR-106b binding sites and to downregulate Mfn2 protein abundance at the post-transcriptional level by luciferase activity assay combined with mutational analysis and immunoblotting. Overexpression of miR-106b resulted in mitochondrial dysfunction and insulin resistance in C2C12 myotubes. MiR-106b was increased in insulin-resistant cultured C2C12 myotubes induced by TNF-α, and accompanied by increasing Mfn2 level, miR-106b loss of function improved mitochondrial function and insulin sensitivity impaired by TNF-α in C2C12 myotubes. In addition, both overexpression and downregulation of miR-106b upregulated peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α and estrogen-related receptor (ERR)-α expression. MiR-106b targeted Mfn2 and regulated skeletal muscle mitochondrial function and insulin sensitivity. Therefor, Inhibition of miR-106b may be a potential new strategy for treating insulin resistance and type 2 diabetes.

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http://dx.doi.org/10.1016/j.mce.2013.08.004DOI Listing
December 2013
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