Metabolomic analysis for hepatic tumors of Hras12V transgenic mice
作者单位：Laboratory animal centerDalian medical University
会议名称：《2017年第十五届中国北方实验动物科技年会》
会议日期：2017年
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
关 键 词：Ras oncogene Hepatocellular carcinoma Metabolomics Transcriptomics
摘 要：Activation of the Ras/MAPK pathway is prevalently involved in the occurrence and development of hepatocellular carcinoma（HCC）.However,its effects on the deregulated cellular metabolic processes involved in HCC in vivo remain *** the present study,a mouse model of HCC induced by hepatocyte-specific expression of the Hras12 V oncogene was investigated using an integrative analysis of metabolomics and transcriptomics *** with the phenotype of abundant lipid droplets in HCC,the lipid biosynthesis in HCC was significantly enhanced by（1） a sufficient supply of acetyl-CoA from enhanced glycolysis and citrate shuttle activity;（2） a sufficient supply of NADPH from enhanced pentose phosphate pathway（PPP） activity;（3） upregulation of key enzymes associated with lipid biosynthesis;and（4） down-regulation of key enzymes associated with bile acid *** addition,glutathione（GSH） was significantly elevated,which may result from a sufficient supply of 5-oxoproline and L-glutamate as well as an enhanced reduction of the process of GSSG being turned into GSH by *** high level of GSH along with elevated Bcl2 and Ucp2 expression may contribute to a normal level of reactive oxygen species（ROS） in *** conclusion,our results suggest that the lipid metabolism,glycolysis,PPP,tricarboxylic acid（TCA） cycle,citrate shuttle activity,bile acid synthesis,and redox homeostasis in the HCC induced by ras oncogene are significantly perturbed,and these altered metabolic processes may play crucial roles in the carcinogenesis,development and pathological characteristics of HCC.