Department of Biochemistry, Dongguk University School of Medicine, Gyeongju 780-714, Republic of Korea.
Biochem Biophys Res Commun. 2013 May 10;434(3):503-8. doi: 10.1016/j.bbrc.2013.03.104. Epub 2013 Apr 11.
MicroRNA (miRNA) is a class of endogenous small noncoding RNA that negatively regulates gene expression at the post-transcriptional level and plays an important role in the pathogenesis of various diseases. However, the identity and role of miRNAs involved in the development of insulin resistance resulting from mitochondrial dysfunction are largely unknown. In this study, mitochondrial dysfunction by genetic or metabolic inhibition induced an impairment of insulin signaling in SK-Hep1 cells via a reduction in the expression of IRS-1 protein. Significant up-regulation of miR-96, which was presumed to target IRS-1 3'UTR, was found in SK-Hep1 cells with mitochondrial dysfunction. Using reporter gene assay we confirmed that miR-96 authentically targeted IRS-1 3'UTR. Furthermore, the ectopic expression of miR-96 caused a substantial decrease in IRS-1 protein expression, and a consequent impairment in insulin signaling. These findings suggest that the up-regulation of miR-96 by mitochondrial dysfunction contributes to the development of insulin resistance by targeting IRS-1 in SK-Hep1 cells.
微小 RNA（miRNA）是一类内源性的小型非编码 RNA，通过在转录后水平负调控基因表达，在各种疾病的发病机制中发挥重要作用。然而，线粒体功能障碍导致胰岛素抵抗的 miRNA 的身份和作用在很大程度上是未知的。在这项研究中，通过遗传或代谢抑制引起的线粒体功能障碍导致 SK-Hep1 细胞中的胰岛素信号受损，这是通过 IRS-1 蛋白表达的减少引起的。在存在线粒体功能障碍的 SK-Hep1 细胞中发现 miR-96 的显著上调，这被认为是针对 IRS-1 3'UTR 的。通过报告基因检测，我们证实 miR-96 可真实地靶向 IRS-1 3'UTR。此外，miR-96 的异位表达导致 IRS-1 蛋白表达大量减少，并导致胰岛素信号受损。这些发现表明，线粒体功能障碍导致 miR-96 的上调，通过靶向 SK-Hep1 细胞中的 IRS-1 导致胰岛素抵抗的发展。
