A biphasic response pattern of lipid metabolomics in the stage progression of hepatitis B virus X tumorigenesis

Chiao Fang Teng, Wen Chuan Hsieh, Ching Wen Yang, Hui Min Su, Ting Fen Tsai, Wang Chou Sung, Wenya Huang, Ih Jen Su

研究成果: Article同行評審

15 引文 斯高帕斯(Scopus)

摘要

Metabolic syndrome has closely linked to the development of human hepatocellular carcinoma (HCC). By using the hepatitis B virus (HBV) X (HBx) transgenic mouse model, we studied the dynamic evolution of serum and liver profiles of lipids and global cDNA expression at different stages of HBx tumorigenesis. We observed that the lipid (triglycerides, cholesterol, and fatty acids) profiles revealed a biphasic response pattern during the progression of HBx tumorigenesis: a small peak at early phase and a large peak or terminal switch at the tumor phase. By analyzing cDNA microarray data, the early peak correlated to the oxidative stress and pro-inflammatory response, which then resolved at the middle phase and were followed by the terminal metabolic switch in the tumor tissues. Five lipid metabolism-related genes, the arachidonate 5-lipoxygenase, lipoprotein lipase, fatty acid binding protein 4, 1-acylglycerol-3-phosphate O-acyltransferase 9, and apolipoprotein A-IV were identified to be significantly activated in HBx transgenic HCCs and further validated in human HBV-related HCCs. Inhibition of these lipid genes could reverse the effect of HBx on lipid biosynthesis and suppress HBx-induced cell proliferation in vitro. Our results support the concept that metabolic syndrome plays an important role in HBV tumorigenesis. The dysregulation of lipid metabolic genes may predict the disease progression to HCC in chronic hepatitis B patients.

原文English
頁(從 - 到)105-114
頁數10
期刊Molecular Carcinogenesis
55
發行號1
DOIs
出版狀態Published - 2016 一月 1

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cancer Research

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