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 CC14 induced liver carcinogenesis in the hepatic-specific SIRT6 HKO mice models and found that hepatic S1RT6 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.
基金
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)
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).