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

被引：105

作者：

Zhang, Ying ^{[1
]}

Yang, Lei ^{[2
,3
]}

Gao, Yuan-Fu ^{[1
]}

Fan, Zhong-Min ^{[1
]}

Cai, Xiao-Yi ^{[1
]}

Liu, Meng-Yuan ^{[1
]}

Guo, Xi-Rong ^{[2
,3
]}

Gao, Chun-Lin ^{[1
]}

Xia, Zheng-Kun ^{[1
]}

机构：

[1] Nanjing Univ Sch Med, Jinling Hosp, Dept Pediat, Nanjing 210002, Jiangsu, Peoples R China

[2] Nanjing Med Univ, Nanjing Maternal & Child Hlth Hosp, Dept Pediat, Nanjing 210004, Jiangsu, Peoples R China

[3] Nanjing Med Univ, Inst Pediat, Nanjing 210029, Jiangsu, Peoples R China

来源：

MOLECULAR AND CELLULAR ENDOCRINOLOGY | 2013年 / 381卷 / 1-2期

基金：

中国国家自然科学基金;

关键词：

C2C12; myotubes; Insulin resistance; MicroRNA-106b; Mitofusin-2; Mitochondrial function; Peroxisome proliferator-activated receptor gamma coactivator-1 alpha; GENOME-WIDE ASSOCIATION; SKELETAL-MUSCLE; ENDOPLASMIC-RETICULUM; 2A GENE; EXPRESSION; GLUCOSE; MFN2; OBESITY; FUSION; ALPHA;

D O I：

10.1016/j.mce.2013.08.004

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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-alpha, and accompanied by increasing Mfn2 level, miR-106b loss of function improved mitochondrial function and insulin sensitivity impaired by TNF-alpha in C2C12 myotubes. In addition, both overexpression and downregulation of miR-106b upregulated peroxisome proliferator-activated receptor gamma coactivator (PGC)-l alpha and estrogen-related receptor (ERR)-alpha 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. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

引用

页码：230 / 240

页数：11

共 38 条

[1]

Expression of Mfn2, the Charcot-Marie-Tooth neuropathy type 2A gene, in human skeletal muscle -: Effects of type 2 diabetes, obesity, weight loss, and the regulatory role of tumor necrosis factor α, and interleukin-6 [J].