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Full Length Article | Open Access

Hepatic SIRT6 deficit promotes liver tumorigenesis in the mice models

Mei Wanga,b,1, Linhua Lanc,1, Fan Yangd,1, Shan Jiangd,1, Haojun Xua, Chengfei Zhanga, Guoren Zhoue( ), Hongping Xiaa,b,e( ), Jinglin Xiac( )
Department of Pathology in the School of Basic Medical Sciences & Sir Run Run Hospital & State Key Laboratory of Reproductive Medicine & Key Laboratory of Antibody Technique of National Health Commission, Nanjing Medical University, Nanjing, Jiangsu 211166, PR China
Department of Immunology, Medical School of Southeast University, Nanjing, Jiangsu 210009, PR China
The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, PR China
The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China
Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu 210009, PR China

Peer review under responsibility of Chongqing Medical University.

1 These authors contributed equally to this work.

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Abstract

SIRT6 belongs to class Ⅲ sirtuin family with NAD+-dependent histone deacetylase activities and controls multiple processes including aging, metabolism and inflammation. In recent years, increasing studies showed tumor suppressor role of SIRT6 in HCC development. We established a two-stage DEN followed CCl4 induced liver carcinogenesis in the hepatic-specific SIRT6 HKO mice models and found that hepatic SIRT6 deficit significantly promotes liver injury and liver cancer through inhibition of the ERK1/2 pathway. SIRT6 was compensatory upregulated in mice tumor tissues and human HCC cells and overexpressed SIRT6 inhibits tumor growth both in vitro and in vivo. Taken together, we provide a useful mouse model for delineating the molecular pathways involved in chronic liver diseases and primary liver cancer and suggest that SIRT6 can be a promising target for HCC therapies.

Keywords

HCCMouse modelERK1/2 pathwayLiver carcinogenesisSIRT6

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Genes & Diseases
Volume 9 Issue 3,
May 2022
Pages 789-796
DOI: 10.1016/j.gendis.2020.08.007
Cite this article:
Wang M, Lan L, Yang F, et al. Hepatic SIRT6 deficit promotes liver tumorigenesis in the mice models. Genes & Diseases, 2022, 9(3): 789-796. https://doi.org/10.1016/j.gendis.2020.08.007

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Received: 28 April 2020
Revised: 23 July 2020
Accepted: 24 August 2020
Published: 02 September 2020
© 2020, Chongqing Medical University.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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