title: MicroRNA-106b induces mitochondrial dysfunction and insulin resistance in C2C12 myotubes by targeting mitofusin-2.
abstract: 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.
authors: Department of Pediatrics, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, People's Republic of China.
authors: Ying
authors: Y
authors: Zhang
authors: Lei
authors: L
authors: Yang
authors: Yuan-Fu
authors: YF
authors: Gao
authors: Zhong-Min
authors: ZM
authors: Fan
authors: Xiao-Yi
authors: XY
authors: Cai
authors: Meng-Yuan
authors: MY
authors: Liu
authors: Xi-Rong
authors: XR
authors: Guo
authors: Chun-Lin
authors: CL
authors: Gao
authors: Zheng-Kun
authors: ZK
authors: Xia
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D020558:GTP Phosphohydrolases / Q000235:genetics* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000502:physiology; D007333:Insulin Resistance; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D008931:Mitochondria, Muscle / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D053140:Organelle Shape; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D034622:RNA Interference; D011960:Receptors, Estrogen / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D020413:3' Untranslated Regions; D020558:GTP Phosphohydrolases; D005947:Glucose; D007328:Insulin; D035683:MicroRNAs; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011960:Receptors, Estrogen; D014157:Transcription Factors; D000097983:ERRalpha Estrogen-Related Receptor; C543896:Mirn106 microRNA, mouse; C485290:Ppargc1a protein, mouse; C488751:Mfn2 protein, mouse
keywords: 3′ UTR; 3′ untranslated region; C2C12 myotubes; DHE; DMEM; Dulbecco’s modified Eagle’s medium; ECL; ERR-α; FACS; GLUT4; IRS-1; Insulin resistance; Mfn2; MicroRNA-106b; Mitochondrial function; Mitofusin-2; PGC-1α; Peroxisome proliferator-activated receptor gamma coactivator-1α; ROS; SDS-PAGE; T2DM; TNF-α; dihydroethidium; enhanced chemiluminescence; estrogen-related receptor-α; fluorescence assisted cell sorting; glucose transporter 4; insulin receptor substrate 1; miR-106b; miRNAs; microRNA-106b; microRNAs; mitochondrial DNA; mitochondrial membrane potential; mitofusin-2; mtDNA; peroxisome proliferator-activated receptor gamma coactivator-1α; reactive oxygen species; sodium dodecyl sulfate-polyacrylamide electrophoresis; tumor necrosis factor-α; type 2 diabetes mellitus; ΔΨ