E2F1-mediated Up-regulation of NCAPG Promotes Hepatocellular Carcinoma Development by Inhibiting Pyroptosis  

作　　者：Cuicui Xiao Jiao Gong Yusheng Jie Weicheng Liang Yan Tai Wei Qin Tongyu Lu Yutian Chong Ziqing Hei Bo Hu Qi Zhang 

机构地区：[1]Biotherapy Center,Third Affiliated Hospital of Sun Yat-sen University,Guangzhou,Guangdong,China [2]Department of Anesthesiology,Third Affiliated Hospital of Sun Yat-sen University,Guangzhou,Guangdong,China [3]Key Laboratory of Liver Disease of Guangdong Province,Third Affiliated Hospital of Sun Yat-sen University,Guangzhou,Guangdong,China [4]Department of Laboratory Medicine,Third Affiliated Hospital of Sun Yat-sen University,Guangzhou,Guangdong,China [5]Department of Infectious Diseases,Third Affiliated Hospital of Sun Yat-sen University,Guangzhou,Guangdong,China [6]Cell-Gene Therapy Translational Medicine Research Center,Third Affiliated Hospital of Sun Yat-sen University,Guangzhou,Guangdong,China [7]Department of Hepatic Surgery,The Third Affiliated Hospital of Sun Yat-sen University,Guangzhou,Guangdong,China

出　　处：《Journal of Clinical and Translational Hepatology》2024年第1期25-35,共11页临床与转化肝病杂志（英文版）

基　　金：supported by the Natural Science Foundation of China(81870449,81670601,81370555,82100693,82170674,81902886,U22A20276);Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme(GDUPS,2017);the Science and Technology Program of Guangzhou,China(201903010039,2019B020228001,202206010072,202102020310,202102010155);International cooperation project of Guangdong science and technology plan(2019B020228001,2020A0505100034);Guangdong Basic and Applied Basic Research Foundation(2022A 1515110316,2020A1515110687);Natural Science Foundation of Guangdong Province,(2022A1515012453);Medical Scientific Research Foundation of Guangdong Province,China,(A2020120)Sun Yat-sen University Clinical Research 5010 Program(2016009).

摘　　要：Background and Aims:As a subunit of the condensin complex,NCAPG has an important role in maintaining chromosome condensation,but its biological function and regulatory mechanism in hepatocellular carcinoma(HCC)remains undefined.Methods:The prognostic ability of NCAPG in HCC patients was examined by univariate and multivariate Cox regression analysis.ROC curves were plotted to compare the predictive ability of NCAPG and AFP.Double luciferase reporter system,and ChIP were used to investigate transcriptional potential of E2F1 to NCAPG.Pyroptosis was observed by scanning electron microscopy.Protein expression of NCAPG,E2F1,and major proteins constituting NLRP3 inflammasome was determined by western blotting and ELISA.An in vivo tumor formation assay was conducted to verify the in vitro results.Results:Up-regulated NCAPG was identified in HCC tissues compared with adjacent tissue and high NCAPG was positively correlated with poor prognosis.Serum NCAPG mRNA level was a prognostic factor in HCC patients and also a diagnostic factor with higher predictive ability compared with AFP[AUROC 0.766(95%CI:0.650–0.881)vs.0.649(95%CI 0.506–0.793)].HBx transfection resulted in concomitant up-regulation of E2F1 and NCAPG.E2F1 significantly increased the activity of luciferase reporter fused with NCAPG reporter,and the interaction of E2F1 and NCAPG gene was confirmed by ChIP.Silencing of E2F1 resulted in significant down-regulation of NCAPG.Knockdown of NCAPG promote pyroptosis mediated by NLRP3 inflammasome activation in multiple HCC cell lines and also suppressed tumorigenesis in vitro.Conclusions:We identified a novel role of NCAPG in the regulation of NLRP3 inflammasome-mediated pyroptosis,which was regulated by its upstream transactivator,E2F1.The role of E2F1-NCAPG-NLRP3 regulation of pyroptosis network may be a potential target in HCC treatment.

关 键 词：NCAPG Hepatocellular carcinoma PYROPTOSIS NLRP3 inflammasome Serum marker circulating RNA. 

分 类 号：R735.7[医药卫生—肿瘤]