title: Hepatitis B virus X protein (HBx)-induced abnormalities of nucleic acid metabolism revealed by (1)H-NMR-based metabonomics.
abstract: Hepatitis B virus X protein (HBx) plays an important role in HBV-related hepatocarcinogenesis; however, mechanisms underlying HBx-mediated carcinogenesis remain unclear. In this study, an NMR-based metabolomics approach was applied to systematically investigate the effects of HBx on cell metabolism. EdU incorporation assay was conducted to examine the effects of HBx on DNA synthesis, an important feature of nucleic acid metabolism. The results revealed that HBx disrupted metabolism of glucose, lipids, and amino acids, especially nucleic acids. To understand the potential mechanism of HBx-induced abnormalities of nucleic acid metabolism, gene expression profiles of HepG2 cells expressing HBx were investigated. The results showed that 29 genes involved in DNA damage and DNA repair were differentially expressed in HBx-expressing HepG2 cells. HBx-induced DNA damage was further demonstrated by karyotyping, comet assay, Western blotting, immunofluorescence and immunohistochemistry analyses. Many studies have previously reported that DNA damage can induce abnormalities of nucleic acid metabolism. Thus, our results implied that HBx initially induces DNA damage, and then disrupts nucleic acid metabolism, which in turn blocks DNA repair and induces the occurrence of hepatocellular carcinoma (HCC). These findings further contribute to our understanding of the occurrence of HCC.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.lastname: Dan Yue
authors.affiliation: Division of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Liuliu
authors.initials: L
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Jinhu
authors.initials: J
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Xi
authors.affiliation: Oncology Medicine Department, Donggang Branch of The First Hospital of Lanzhou University, 730000, PR China.
authors.forename: Liping
authors.initials: L
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Su
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Shao
authors.affiliation: Department of Pathology, West China Second University Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Anliang
authors.initials: A
authors.lastname: Huang
authors.affiliation: School of Medicine/Collaborative Innovation Center for Biotherapy, Nankai University, Tianjin 300071, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Xiang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Cheng
mesh_terms: D004249:DNA Damage; D020869:Gene Expression Profiling; D056945:Hep G2 Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D055432:Metabolomics; D009696:Nucleic Acids / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D009696:Nucleic Acids; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein