Mitochondria-related miR-141-3p contributes to mitochondrial dysfunction in HFD-induced obesity by inhibiting PTEN

线粒体相关 miR-141-3p 通过抑制 PTEN 导致 HFD 诱发的肥胖中的线粒体功能障碍

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作者:Juan Ji, Yufeng Qin, Jing Ren, Chuncheng Lu, Rong Wang, Xiuliang Dai, Ran Zhou, Zhenyao Huang, Miaofei Xu, Minjian Chen, Wei Wu, Ling Song, Hongbing Shen, Zhibin Hu, Dengshun Miao, Yankai Xia, Xinru Wang

Abstract

Mitochondria-related microRNAs (miRNAs) have recently emerged as key regulators of cell metabolism and can modulate mitochondrial fusion and division. In order to investigate the roles of mitochondria-related miRNAs played in obesity, we conducted comprehensive molecular analysis in vitro and in vivo. Based on high-fat-diet (HFD) induced obese mice, we found that hepatic mitochondrial function was markedly altered. Subsequently, we evaluated the expression levels of selected mitochondria-related miRNAs and found that miR-141-3p was up-regulated strikingly in HFD mice. To further verify the role of miR-141-3p in obesity, we carried out gain-and-loss-of-function study in human HepG2 cells. We found that miR-141-3p could modulate ATP production and induce oxidative stress. Through luciferase report gene assay, we identified that phosphatase and tensin homolog (PTEN) was a target of miR-141-3p. Inhibiting PTEN could alter the mitochondrial function, too. Our study suggested that mitochondria-related miR-141-3p induced mitochondrial dysfunction by inhibiting PTEN.

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