A biphasic response pattern of lipid metabolomics in the stage progression of hepatitis B virus X tumorigenesis
Chiao-Fang Teng
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan, Taiwan
Search for more papers by this authorWen-Chuan Hsieh
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan, Taiwan
Search for more papers by this authorChing-Wen Yang
Institute of Basic Medical Research, National Cheng Kung University College of Medicine, Tainan, Taiwan
Search for more papers by this authorHui-Min Su
Department of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan
Search for more papers by this authorTing-Fen Tsai
Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan
Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan, Taiwan
Search for more papers by this authorWang-Chou Sung
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan, Taiwan
Search for more papers by this authorWenya Huang
Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University College of Medicine, Tainan, Taiwan
Search for more papers by this authorCorresponding Author
Ih-Jen Su
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan, Taiwan
Institute of Basic Medical Research, National Cheng Kung University College of Medicine, Tainan, Taiwan
Correspondence to: Ih-Jen Su, National Health Research Institutes, 367, Sheng-Li Road, Tainan 704, Taiwan.
Search for more papers by this authorChiao-Fang Teng
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan, Taiwan
Search for more papers by this authorWen-Chuan Hsieh
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan, Taiwan
Search for more papers by this authorChing-Wen Yang
Institute of Basic Medical Research, National Cheng Kung University College of Medicine, Tainan, Taiwan
Search for more papers by this authorHui-Min Su
Department of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan
Search for more papers by this authorTing-Fen Tsai
Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan
Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan, Taiwan
Search for more papers by this authorWang-Chou Sung
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan, Taiwan
Search for more papers by this authorWenya Huang
Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University College of Medicine, Tainan, Taiwan
Search for more papers by this authorCorresponding Author
Ih-Jen Su
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan, Taiwan
Institute of Basic Medical Research, National Cheng Kung University College of Medicine, Tainan, Taiwan
Correspondence to: Ih-Jen Su, National Health Research Institutes, 367, Sheng-Li Road, Tainan 704, Taiwan.
Search for more papers by this authorAbstract
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. © 2015 Wiley Periodicals, Inc.
Supporting Information
Additional supporting information may be found in the online version of this article at the publisher's web-site.
| Filename | Description |
|---|---|
| mc22266-sup-0001-SupFig-S1.tif464.6 KB |
Figure S1: Silencing efficacy and specificity of siRNAs against ALOX5, LPL, CIDEA, FABP4, AGPAT9, and APOA4: HuH-7 cells were treated with the control siRNA (Ctrl-siRNA) or siRNAs against ALOX5 (siALOX5, A), LPL (siLPL, B), CIDEA (siCIDEA, C), FABP4 (siFABP4, D), AGPAT9 (siAGPAT9, E), and APOA4 (siAPOA4, F) in final concentrations of 25, 50, and 100 nM. |
| mc22266-sup-0001-SupTab-S1-S2.doc57.5 KB |
Table S1: cDNA microarray analysis of gene clusters associated with stress, inflammation, genomic instability, and cell proliferation in HBx transgenic livers. Table S2: cDNA microarray analysis of lipid gene expression profiles in HBx transgenic livers. |
| mc22266-sup-0001-SupFigLeg-S1.doc23 KB | Supplementary Figure Legends. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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