Metabolomic analysis for hepatic tumors of Hras12V transgenic mice
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 unknown.In the present study,a mouse model of HCC induced by hepatocyte-specific expression of the Hras12V oncogene was investigated using an integrative analysis of metabolomics and transcriptomics data.Consistent 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 biosynthesis.In 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 NADPH.The high level of GSH along with elevated Bcl2 and Ucp2 expression may contribute to a normal level of reactive oxygen species(ROS)in HCC.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.
Ras oncogene Hepatocellular carcinoma Metabolomics Transcriptomics
Tingting Fan Zhuona Rong Juan Li Fujin Wang Jingyu Wang Aiguo Wang
Laboratory animal center,Dalian medical University,Dalian,Liaoning 116044,P.R.China
国内会议
呼和浩特
英文
270-278
2017-09-12（万方平台首次上网日期，不代表论文的发表时间）