miR-26a enhances autophagy to protect against ethanol-induced acute liver injury

Verfasser / Beitragende:
[Weidong Han, Xianghui Fu, Jiansheng Xie, Zhipeng Meng, Ying Gu, Xichun Wang, Ling Li, Hongming Pan, Wendong Huang]
Ort, Verlag, Jahr:
2015
Enthalten in:
Journal of Molecular Medicine, 93/9(2015-09-01), 1045-1055
Format:
Artikel (online)
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024 7 0 |a 10.1007/s00109-015-1282-2  |2 doi 
035 |a (NATIONALLICENCE)springer-10.1007/s00109-015-1282-2 
245 0 0 |a miR-26a enhances autophagy to protect against ethanol-induced acute liver injury  |h [Elektronische Daten]  |c [Weidong Han, Xianghui Fu, Jiansheng Xie, Zhipeng Meng, Ying Gu, Xichun Wang, Ling Li, Hongming Pan, Wendong Huang] 
520 3 |a 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. Key messages: • 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. 
540 |a The Author(s), 2015 
690 7 |a miR-26a  |2 nationallicence 
690 7 |a Autophagy  |2 nationallicence 
690 7 |a Hepatic steatosis  |2 nationallicence 
690 7 |a Mitogen-activated protein kinases  |2 nationallicence 
690 7 |a Ethanol binge  |2 nationallicence 
690 7 |a 3′-UTR : 3′ untranslated region  |2 nationallicence 
690 7 |a miRNAs : MicroRNAs  |2 nationallicence 
690 7 |a miR-26a : MicroRNA 26a  |2 nationallicence 
690 7 |a MAPKs : Mitogen-activated protein kinases  |2 nationallicence 
690 7 |a LDs : Lipid droplets  |2 nationallicence 
690 7 |a mRNAs : Messenger RNAs  |2 nationallicence 
690 7 |a CQ : Chloroquine  |2 nationallicence 
690 7 |a tf-LC3 : Tandem fluorescent-tagged LC3  |2 nationallicence 
690 7 |a PCR : Real-time polymerase chain reaction  |2 nationallicence 
690 7 |a ALT : Alanine aminotransferase  |2 nationallicence 
690 7 |a TEM : Transmission electron microscopy  |2 nationallicence 
700 1 |a Han  |D Weidong  |u Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, 3 East Qingchun Road, 310016, Hangzhou, Zhejiang, China  |4 aut 
700 1 |a Fu  |D Xianghui  |u 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, 91010, Duarte, CA, USA  |4 aut 
700 1 |a Xie  |D Jiansheng  |u Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, 3 East Qingchun Road, 310016, Hangzhou, Zhejiang, China  |4 aut 
700 1 |a Meng  |D Zhipeng  |u 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, 91010, Duarte, CA, USA  |4 aut 
700 1 |a Gu  |D Ying  |u 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, 91010, Duarte, CA, USA  |4 aut 
700 1 |a Wang  |D Xichun  |u 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, 91010, Duarte, CA, USA  |4 aut 
700 1 |a Li  |D Ling  |u 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, 91010, Duarte, CA, USA  |4 aut 
700 1 |a Pan  |D Hongming  |u Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, 3 East Qingchun Road, 310016, Hangzhou, Zhejiang, China  |4 aut 
700 1 |a Huang  |D Wendong  |u 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, 91010, Duarte, CA, USA  |4 aut 
773 0 |t Journal of Molecular Medicine  |d Springer Berlin Heidelberg  |g 93/9(2015-09-01), 1045-1055  |x 0946-2716  |q 93:9<1045  |1 2015  |2 93  |o 109 
856 4 0 |u https://doi.org/10.1007/s00109-015-1282-2  |q text/html  |z Onlinezugriff via DOI 
898 |a BK010053  |b XK010053  |c XK010000 
900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s00109-015-1282-2  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Han  |D Weidong  |u Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, 3 East Qingchun Road, 310016, Hangzhou, Zhejiang, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Fu  |D Xianghui  |u 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, 91010, Duarte, CA, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Xie  |D Jiansheng  |u Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, 3 East Qingchun Road, 310016, Hangzhou, Zhejiang, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Meng  |D Zhipeng  |u 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, 91010, Duarte, CA, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Gu  |D Ying  |u 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, 91010, Duarte, CA, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Wang  |D Xichun  |u 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, 91010, Duarte, CA, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Li  |D Ling  |u 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, 91010, Duarte, CA, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Pan  |D Hongming  |u Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, 3 East Qingchun Road, 310016, Hangzhou, Zhejiang, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Huang  |D Wendong  |u 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, 91010, Duarte, CA, USA  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Journal of Molecular Medicine  |d Springer Berlin Heidelberg  |g 93/9(2015-09-01), 1045-1055  |x 0946-2716  |q 93:9<1045  |1 2015  |2 93  |o 109