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

• Published in: Molecular and cellular endocrinology 2013-12, Vol.381 (1-2), p.230-240
• Main Authors: Zhang, Ying, Yang, Lei, Gao, Yuan-Fu, Fan, Zhong-Min, Cai, Xiao-Yi, Liu, Meng-Yuan, Guo, Xi-Rong, Gao, Chun-Lin, Xia, Zheng-Kun
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions; Animals; Base Sequence; Binding Sites; C2C12 myotubes; Cell Line; Correlation; Diabetes; ERRalpha Estrogen-Related Receptor; Glucose - metabolism; GTP Phosphohydrolases - genetics; GTP Phosphohydrolases - metabolism; Insulin; Insulin - physiology; Insulin Resistance; Mice; MicroRNA-106b; MicroRNAs - physiology; Mitochondria, Muscle - physiology; Mitochondrial function; Mitofusin-2; Muscle Fibers, Skeletal - metabolism; Muscles; Organelle Shape; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Peroxisome proliferator-activated receptor gamma coactivator-1α; Proteins; Receptors; Receptors, Estrogen - metabolism; RNA Interference; Strategy; Transcription Factors - metabolism
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2013.08.004

•MiR-106b gain of function induces mitochondrial dysfunction and insulin resistance in C2C12 myotubes by targeting Mfn2.•MiR-106b participates in TNF-α-induced mitochondrial injury and insulin resistance by regulating Mfn2.•These results suggest that miR-106b may represent a potential therapeutic target for the treatment of insulin resistance and type 2 diabetes. 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.