Lu XF, Zhou YJ, Zhang L, Ji HJ, Li L, Shi YJ, Bu H. Loss of Dicer1 impairs hepatocyte survival and leads to chronic inflammation and progenitor cell activation. World J Gastroenterol 2015; 21(21): 6591-6603 [PMID: 26074697 DOI: 10.3748/wjg.v21.i21.6591]
Corresponding Author of This Article
Yu-Jun Shi, MD, PhD, Laboratory of Pathology, West China Hospital, Sichuan University, 37 Wainan Guoxuexiang, Chengdu 610041, Sichuan Province, China. shiyujun@scu.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
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Lu XF, Zhou YJ, Zhang L, Ji HJ, Li L, Shi YJ, Bu H. Loss of Dicer1 impairs hepatocyte survival and leads to chronic inflammation and progenitor cell activation. World J Gastroenterol 2015; 21(21): 6591-6603 [PMID: 26074697 DOI: 10.3748/wjg.v21.i21.6591]
World J Gastroenterol. Jun 7, 2015; 21(21): 6591-6603 Published online Jun 7, 2015. doi: 10.3748/wjg.v21.i21.6591
Loss of Dicer1 impairs hepatocyte survival and leads to chronic inflammation and progenitor cell activation
Xu-Feng Lu, Yong-Jie Zhou, Lei Zhang, Hong-Jie Ji, Li Li, Yu-Jun Shi, Hong Bu
Xu-Feng Lu, Yong-Jie Zhou, Lei Zhang, Hong-Jie Ji, Li Li, Yu-Jun Shi, Hong Bu, Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Xu-Feng Lu, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Hong Bu, Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Author contributions: Lu XF, Shi YJ and Bu H designed the research; Lu XF performed the research; Zhou YJ and Zhang L contributed analytic tools; Ji HJ and Li L analyzed the data; and Lu XF, Shi YJ and Bu H wrote the paper; all authors read and approved the final manuscript.
Supported by National Key Clinical Project, and National Sciences; and Technology Major Project of China, No. 2012ZX10002-017.
Ethics approval: This study was reviewed and approved by the ethic committee of the West China Hospital of Sichuan University’s Institutional Review Board.
Institutional animal care and use committee: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the West China Hospital of Sichuan University (IACUC-No. S200904-P001).
Conflict-of-interest: The authors declare that they have no conflict of interest or financial interests.
Data sharing: No additional data are available.
Correspondence to: Yu-Jun Shi, MD, PhD, Laboratory of Pathology, West China Hospital, Sichuan University, 37 Wainan Guoxuexiang, Chengdu 610041, Sichuan Province, China. shiyujun@scu.edu.cn
Telephone: +86-28-85164030 Fax: +86-28-85164034
Received: November 7, 2014 Peer-review started: November 8, 2014 First decision: December 11, 2014 Revised: December 22, 2014 Accepted: January 8, 2015 Article in press: January 8, 2015 Published online: June 7, 2015 Processing time: 215 Days and 20.5 Hours
Core Tip
Core tip: MicroRNAs (miRNAs) play a critical role in the regulation of multiple biological genes in the liver. The liver-specific loss of Dicer1, an endoribonuclease essential for precursor miRNAs maturation, results in liver injury and spontaneous development of hepatocellular carcinoma (HCC); however, the gradual histological changes involved in these processes have not been completely characterized. In contrast to previous reports, we found that Dicer1 inactivation causes typical chronic liver injury characterized by profound hepatocyte apoptosis, continuous liver necrosis, active compensatory proliferation, noticeable triad inflammation, progressive liver fibrosis, significant progenitor activation, and spontaneous hepatocarcinogenesis. Our work provides new insights into the role of miRNA in liver injury and HCC development. These results may also aid in the development of a miRNA therapeutic strategy for the prevention and treatment of HCC.
