Hepatic SIRT6 deficit promotes liver tumorigenesis in the mice models

作者全名："Wang, Mei; Lan, Linhua; Yang, Fan; Jiang, Shan; Xu, Haojun; Zhang, Chengfei; Zhou, Guoren; Xia, Hongping; Xia, Jinglin"

作者地址："[Wang, Mei; Xu, Haojun; Zhang, Chengfei; Xia, Hongping] Nanjing Med Univ, Dept Pathol, Sch Basic Med Sci, Nanjing 211166, Jiangsu, Peoples R China; [Wang, Mei; Xu, Haojun; Zhang, Chengfei; Xia, Hongping] Nanjing Med Univ, Sir Run Run Hosp, Nanjing 211166, Jiangsu, Peoples R China; [Wang, Mei; Xu, Haojun; Zhang, Chengfei; Xia, Hongping] Nanjing Med Univ, State Key Lab Reprod Med, Nanjing 211166, Jiangsu, Peoples R China; [Wang, Mei; Xu, Haojun; Zhang, Chengfei; Xia, Hongping] Nanjing Med Univ, Key Lab Antibody Tech, Natl Hlth Commiss, Nanjing 211166, Jiangsu, Peoples R China; [Wang, Mei; Xia, Hongping] Southeast Univ, Dept Immunol, Med Sch, Nanjing 210009, Jiangsu, Peoples R China; [Lan, Linhua; Xia, Jinglin] Wenzhou Med Univ, Affiliated Hosp 1, Wenzhou 325000, Zhejiang, Peoples R China; [Yang, Fan; Jiang, Shan] Chongqing Med Univ, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Zhou, Guoren; Xia, Hongping] Nanjing Med Univ, Jiangsu Canc Hosp, Affiliated Canc Hosp, Nanjing 210009, Jiangsu, Peoples R China; [Zhou, Guoren; Xia, Hongping] Nanjing Med Univ, Jiangsu Inst Canc Res, Affiliated Canc Hosp, Nanjing 210009, Jiangsu, Peoples R China"

通信作者："Xia, HP (通讯作者)，Nanjing Med Univ, Dept Pathol, Sch Basic Med Sci, Nanjing 211166, Jiangsu, Peoples R China.; Zhou, GR (通讯作者)，Jiangsu Canc Hosp, Dept Oncol, Nanjing 210009, Jiangsu, Peoples R China.; Xia, JL (通讯作者)，Wenzhou Med Univ, Dept Intervent Radiol, Affiliated Hosp 1, Wenzhou 325000, Zhejiang, Peoples R China."

来源：GENES & DISEASES

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000805331400019

JCR分区：Q1

影响因子：6.8

年份：2022

卷号：9

期号：3

开始页：789

结束页：796

文献类型：Article

关键词：ERK1/2 pathway; HCC; Liver carcinogenesis; Mouse model; SIRT6

摘要："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 CCE4 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 up-regulated 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. Copyright (C) 2020, Chongqing Medical University. Production and hosting by Elsevier B.V."

基金机构："National Natural Science Foundation of China [81902803, 81972233]; Overseas Young Talents Project of China [(2018)2015]; Science and Technology Grant [BE2019758]; Natural Science Foundation of Jiangsu Province [BK20190657]; Southeast University-Nanjing Medical University Cooperative Research Project [2242018K3DN33]; Fund of Nanjing Medical University; China Scholarship Council [201906090247]"

基金资助正文："This study was supported grants from the National Natural Science Foundation of China (No. 81902803, 81972233), the Overseas Young Talents Project of China, ""Innovative and Entrepreneurial Team"" (No. (2018)2015), Science and Technology Grant (No. BE2019758) and the Natural Science Foundation (No. BK20190657) of Jiangsu Province, Southeast University-Nanjing Medical University Cooperative Research Project (No. 2242018K3DN33), Fund of Nanjing Medical University and the China Scholarship Council (No. 201906090247)."