Time serial transcriptome reveals Cyp2c29 as a key gene in hepatocellular carcinoma development  

作　　者：Qi Wang Qin Tang Lijun Zhao Qiong Zhang Yuxin Wu Hui Hu Lanlan Liu Xiang Liu Yanhong Zhu Anyuan Guo Xiangliang Yang 

机构地区：[1]College of Life Science and Technology,Huazhong University of Science and Technology,Wuhan 430074,China [2]Experimental Transplantation and Immunology Branch,National Cancer Institute,National Institutes of Health,Bethesda,MD 20892,USA

出　　处：《Cancer Biology & Medicine》2020年第2期401-417,共17页癌症生物学与医学（英文版）

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).

摘　　要：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.

关 键 词：Cyp2c29 hepatocellular carcinoma NF-KB PROLIFERATION time series gene expression 

分 类 号：R735.7[医药卫生—肿瘤]