Objective:Hepatocellular carcinoma(HCC)is a severely lethal cancer that usually originates from chronic liver injury and inflammation.Although progress on diagnosis and treatment is obvious,the cause of HCC remains un...Objective:Hepatocellular carcinoma(HCC)is a severely lethal cancer that usually originates from chronic liver injury and inflammation.Although progress on diagnosis and treatment is obvious,the cause of HCC remains unclear.In this study,we sought to determine key genes in HCC development.Methods:To identify key regulators during HCC progression,we performed transcriptome sequencing to obtain time series gene expression data from a mouse model with diethylnitrosamine-induced liver tumors and further verified gene expression and function in vitro and in vivo.Results:Among the differentially expressed genes,Cyp2c29 was continuously downregulated during HCC progression.Overexpression of Cyp2c29 suppressed N F-kB activation and proinflammatory cytokine production by increasing the production o f 14,15-epoxyeicosatrienoic acid in vitro.Furthermore,overexpression of Cyp2c29 in vivo protected against liver inflammation in mouse models of liver injury induced by both acetaminophen and CC14.Two human homologs of mouse Cyp2c29,CYP2C8 and CYP2C9,were found to be downregulated in human HCC progression,and their expression was positively correlated with overall survival in patients with HCC(significance:P=0.046 and 0.0097,respectively).Conclusions:Collectively,through systematic analysis and verification,we determined that C yp2c29 is a novel gene involved in liver injury and inflammation,which may be a potential biomarker for HCC prevention and prognosis determination.展开更多
基金grants from The National Key Research and Development Program of China(Grant No.2017YFA0700403)National Natural Science Foundation of China(Grant Nos.81573013,31822030,and 31771458)National Basic Research Program of China(Grant No.2018YFA0208903).
文摘Objective:Hepatocellular carcinoma(HCC)is a severely lethal cancer that usually originates from chronic liver injury and inflammation.Although progress on diagnosis and treatment is obvious,the cause of HCC remains unclear.In this study,we sought to determine key genes in HCC development.Methods:To identify key regulators during HCC progression,we performed transcriptome sequencing to obtain time series gene expression data from a mouse model with diethylnitrosamine-induced liver tumors and further verified gene expression and function in vitro and in vivo.Results:Among the differentially expressed genes,Cyp2c29 was continuously downregulated during HCC progression.Overexpression of Cyp2c29 suppressed N F-kB activation and proinflammatory cytokine production by increasing the production o f 14,15-epoxyeicosatrienoic acid in vitro.Furthermore,overexpression of Cyp2c29 in vivo protected against liver inflammation in mouse models of liver injury induced by both acetaminophen and CC14.Two human homologs of mouse Cyp2c29,CYP2C8 and CYP2C9,were found to be downregulated in human HCC progression,and their expression was positively correlated with overall survival in patients with HCC(significance:P=0.046 and 0.0097,respectively).Conclusions:Collectively,through systematic analysis and verification,we determined that C yp2c29 is a novel gene involved in liver injury and inflammation,which may be a potential biomarker for HCC prevention and prognosis determination.
