Ji Juan, Qin Yufeng, Ren Jing, Lu Chuncheng, Wang Rong, Dai Xiuliang, Zhou Ran, Huang Zhenyao, Xu Miaofei, Chen Minjian, Wu Wei, Song Ling, Shen Hongbing, Hu Zhibin, Miao Dengshun, Xia Yankai, Wang Xinru
State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China.
Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
Sci Rep. 2015 Nov 9;5:16262. doi: 10.1038/srep16262.
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.
线粒体相关的微小RNA（miRNA）最近已成为细胞代谢的关键调节因子，并且可以调节线粒体的融合与分裂。为了研究线粒体相关miRNA在肥胖症中所起的作用，我们在体外和体内进行了全面的分子分析。基于高脂饮食（HFD）诱导的肥胖小鼠，我们发现肝脏线粒体功能发生了显著改变。随后，我们评估了所选线粒体相关miRNA的表达水平，发现miR-141-3p在HFD小鼠中显著上调。为了进一步验证miR-141-3p在肥胖症中的作用，我们在人肝癌细胞系HepG2中进行了功能获得和缺失研究。我们发现miR-141-3p可以调节ATP生成并诱导氧化应激。通过荧光素酶报告基因检测，我们确定磷酸酶和张力蛋白同源物（PTEN）是miR-141-3p的一个靶标。抑制PTEN也会改变线粒体功能。我们的研究表明，线粒体相关的miR-141-3p通过抑制PTEN诱导线粒体功能障碍。
