The function of targeted host genes determines the oncogenicity of HBV integration in hepatocellular carcinoma
Xiaojun Li a, 1,
Jiangbo Zhang a, 1,
Ziwei Yang a,
Jingting Kang a,
Suzhen Jiang b,
Ting Zhang a,
Tingting Chen a,
Meng Li a,
Xiangmei Chen a, Corresponding author contact information, E-mail the corresponding author,
Malcolm A. McCrae c,
Hui Zhuang a,
Fengmin Lu a, Corresponding author contact information, E-mail the corresponding author
a Department of Microbiology& Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, P. R. China
b Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, Beijing, P. R. China
c The Pirbright Institute, Pirbright, UK
Abstract
Background & aims
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) 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) were 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 are 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. 作者: StephenW 时间: 2013-12-22 13:56