title: The function of targeted host genes determines the oncogenicity of HBV integration in hepatocellular carcinoma.
abstract: OBJECTIVE
  Although hepatitis B virus (HBV) integration into the human genome has been considered as one of the major causative factors to hepatocarcinogenesis, the underlying mechanism(s) was still elusive. Here we investigate the essential difference(s) of HBV integration between HCC tumor and adjacent non-tumor tissues and explore the factor(s) that determine the oncogenicity of HBV integration.
  
  
  METHODS
  1115 HBV integration sites were collected from four recent studies. Functional annotation analysis of integration targeted host genes (ITGs) was performed using DAVID based on Gene Ontology and KEGG pathway databases. Array-based expression profiles, real-time qPCR and western blot were used to detect the expression of recurrent integration targeted genes (RTGs). The biological consequences of the overexpression of UBXN8 in 8 HCC cell lines were studied in vitro.
  
  
  RESULTS
  HBV is prone to integrate in genic regions (exons, introns, and promoters) and gene-dense regions. Functional annotation analysis reveals that, compared to those in adjacent non-tumor tissues, ITGs in HCC tumor tissues were significantly enriched in functional terms related to negative regulation of cell death, transcription regulation, development and differentiation, and cancer related pathways. 32% of the 75 RTGs identified in this analysis expressed abnormally in HCC tissues. UBXN8, one of the RTGs, was identified as a new tumor suppressor candidate which functions in a TP53 dependent manner.
  
  
  CONCLUSIONS
  The oncogenicity of HBV integration was determined, to some extend by the function of HBV integration targeted host genes in HCC.
authors.affiliation: Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China.
authors.forename: Jiangbo
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China.
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China.
authors.forename: Jingting
authors.initials: J
authors.lastname: Kang
authors.affiliation: Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, Beijing, PR China.
authors.forename: Suzhen
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, Henan, PR China.
authors.forename: Quanjun
authors.initials: Q
authors.lastname: Lv
authors.affiliation: Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China. Electronic address: xm_chen6176@bjmu.edu.cn.
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Chen
authors.affiliation: The Pirbright Institute, Pirbright, UK.
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: McCrae
authors.affiliation: Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhuang
authors.affiliation: Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China. Electronic address: lu.fengmin@hsc.pku.edu.cn.
authors.forename: Fengmin
authors.initials: F
authors.lastname: Lu
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002472:Cell Transformation, Viral / Q000235:genetics; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D015894:Genome, Human; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000235:genetics* / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D008099:Liver / Q000821:virology; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology*; D011506:Proteins / Q000235:genetics; D016662:Virus Integration / Q000235:genetics*
chemical_list: D011506:Proteins; C104829:UBXN8 protein, human
keywords: Functional annotation analysis; HBV integration; Hepatitis B virus; Hepatocellular carcinoma; UBXN8