Previous studies have shown that PRDX5 and Nrf2 are antioxidant proteins related to abnormal reactive oxidative species(ROS).PRDX5 and Nrf2 play a critical role in the progression of inflammations and tumors.The combin...Previous studies have shown that PRDX5 and Nrf2 are antioxidant proteins related to abnormal reactive oxidative species(ROS).PRDX5 and Nrf2 play a critical role in the progression of inflammations and tumors.The combination of PRDX5 and Nrf2 was examined by Co-immunoprecipitation,western blotting and Immunohistochemistry.H2O2 was applied to affect the production of ROS and induced multi-resistant protein 1(MRP1)expression in NSCLC cells.The zebrafish models mainly investigated the synergistic effects of PRDX5 and Nrf2 on lung cancer drug resistance under oxidative stress.We showed that PRDX5 and Nrf2 form a complex and significantly increase the NSCLC tissues compared to adjacent tissues.The oxidative stress improved the combination of PRDX5 and Nrf2.We demonstrated that the synergy between PRDX5 and Nrf2 is positively related to the proliferation and drug resistance of NSCLC cells in the zebrafish models.In conclusion,our data indicated that PRDX5 could bind to Nrf2 and has a synergistic effect with Nrf2.Meanwhile,in the zebrafish models,PRDX5 and Nrf2 have significant regulatory impacts on lung cancer progression and drug resistance activities under oxidative stress.展开更多
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 ...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.展开更多
基金supported by grants from National Natural Science Foundation of China(82273162)The Recruitment Program of Overseas High-Level Young Talents,Jiangsu Cancer Hospital Spark Fundamental Research Special Fund(ZJ202103)+1 种基金Jiangsu Province Health Care and Elderly Health Research Key Topics(LKZ2022007)Funding of Postdoctoral Funding of Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University and Xisike Clinical Oncology Research Foundation(Y-HS202102-0177).
文摘Previous studies have shown that PRDX5 and Nrf2 are antioxidant proteins related to abnormal reactive oxidative species(ROS).PRDX5 and Nrf2 play a critical role in the progression of inflammations and tumors.The combination of PRDX5 and Nrf2 was examined by Co-immunoprecipitation,western blotting and Immunohistochemistry.H2O2 was applied to affect the production of ROS and induced multi-resistant protein 1(MRP1)expression in NSCLC cells.The zebrafish models mainly investigated the synergistic effects of PRDX5 and Nrf2 on lung cancer drug resistance under oxidative stress.We showed that PRDX5 and Nrf2 form a complex and significantly increase the NSCLC tissues compared to adjacent tissues.The oxidative stress improved the combination of PRDX5 and Nrf2.We demonstrated that the synergy between PRDX5 and Nrf2 is positively related to the proliferation and drug resistance of NSCLC cells in the zebrafish models.In conclusion,our data indicated that PRDX5 could bind to Nrf2 and has a synergistic effect with Nrf2.Meanwhile,in the zebrafish models,PRDX5 and Nrf2 have significant regulatory impacts on lung cancer progression and drug resistance activities under oxidative stress.
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)+2 种基金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).
文摘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.
