title: MiR-26a enhances autophagy to protect against ethanol-induced acute liver injury.
abstract: Autophagy is a process for the turnover of intracellular organelles and molecules during stress responses. microRNAs (miRNAs) are small, non-coding endogenous RNAs that may regulate almost every cellular process. However, the roles of miRNAs in autophagy are still poorly understood. In this study, we show that miR-26a enhances autophagy in both culture cells and the mouse liver. Hepatic overexpression of miR-26a in mice alleviated ethanol-induced hepatic steatosis and liver injury. Overexpression of miR-26a increased the expression of the autophagy mediator Beclin-1, which is regulated by mitogen-activated protein kinases (MAPKs). We identified DUSP4 and DUSP5, two MAPKs inhibitors, as direct targets of miR-26a. We further demonstrated that miR-26a targeted the 3'-UTRs of several other negative regulators of autophagy. Our results thus identify a novel miRNA-mediated mechanism that enhances cytoprotective autophagy in the liver.
  
  
  CONCLUSIONS
  • miR-26a enhances autophagy in liver cells. • Hepatic overexpression of miR-26a in mice alleviates ethanol-induced liver injury. • Overexpression of miR-26a increases the expression of autophagy mediator Beclin-1. • DUSP4 and DUSP5, two MAPKs inhibitors, were identified as direct targets of miR-26a.
authors: Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, Zhejiang, 310016, China.|Division of Molecular Diabetes Research, Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope National Medical Center, 1500 E. Duarte Road, Duarte, CA, 91010, USA.
authors: Weidong
authors: W
authors: Han
authors: Division of Molecular Diabetes Research, Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope National Medical Center, 1500 E. Duarte Road, Duarte, CA, 91010, USA. xfu@scu.edu.cn.|Division of Endocrinology and Metabolism, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. xfu@scu.edu.cn.|Collaborative Innovation Center of Biotherapy, Chengdu, 610041, Sichuan, China. xfu@scu.edu.cn.
authors: Xianghui
authors: X
authors: Fu
authors: Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, Zhejiang, 310016, China.
authors: Jiansheng
authors: J
authors: Xie
authors: Division of Molecular Diabetes Research, Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope National Medical Center, 1500 E. Duarte Road, Duarte, CA, 91010, USA.
authors: Zhipeng
authors: Z
authors: Meng
authors: Division of Molecular Diabetes Research, Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope National Medical Center, 1500 E. Duarte Road, Duarte, CA, 91010, USA.
authors: Ying
authors: Y
authors: Gu
authors: Division of Molecular Diabetes Research, Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope National Medical Center, 1500 E. Duarte Road, Duarte, CA, 91010, USA.
authors: Xichun
authors: X
authors: Wang
authors: Division of Molecular Diabetes Research, Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope National Medical Center, 1500 E. Duarte Road, Duarte, CA, 91010, USA.
authors: Ling
authors: L
authors: Li
authors: Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, Zhejiang, 310016, China. hongmingpan@gmail.com.
authors: Hongming
authors: H
authors: Pan
authors: Division of Molecular Diabetes Research, Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope National Medical Center, 1500 E. Duarte Road, Duarte, CA, 91010, USA. whuang@coh.org.
authors: Wendong
authors: W
authors: Huang
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000502:physiology; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000517:prevention & control; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*
chemical_list: D035683:MicroRNAs; C543693:Mirn26 microRNA, mouse; D000431:Ethanol
keywords: Autophagy; Ethanol binge; Hepatic steatosis; Mitogen-activated protein kinases; miR-26a