Constructing the HBV-human protein interaction network to understand the relationship between HBV and hepatocellular carcinoma

BackgroundEpidemiological studies have clearly validated the association between hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). Patients with chronic HBV infection are at increased risk of HCC, in particular those with active liver disease and cirrhosis.MethodsWe catalogued all published interactions between HBV and human proteins, identifying 250 descriptions of HBV and human protein interactions and 146 unique human proteins that interact with HBV proteins by text mining.ResultsIntegration of this data set into a reconstructed human interactome showed that cellular proteins interacting with HBV are made up of core proteins that are interconnected with many pathways. A global analysis based on functional annotation highlighted the enrichment of cellular pathways targeted by HBV.ConclusionsBy connecting the cellular proteins targeted by HBV, we have constructed a central network of proteins associated with hepatocellular carcinoma, which might be to regard as the basis of a detailed map for tracking new cellular interactions, and guiding future investigations.

[1]  G. Gores,et al.  Hepatocellular carcinoma: molecular pathways and new therapeutic targets. , 2005, Seminars in liver disease.

[2]  G. Abou-Alfa,et al.  The impact of new data in the treatment of advanced hepatocellular carcinoma , 2008, Current oncology reports.

[3]  Lilia M. Iakoucheva,et al.  Intrinsic Disorder Is a Common Feature of Hub Proteins from Four Eukaryotic Interactomes , 2006, PLoS Comput. Biol..

[4]  M. Lai,et al.  Novel Autoregulatory Function of Hepatitis B Virus M Protein on Surface Gene Expression* , 2005, Journal of Biological Chemistry.

[5]  L. Lin,et al.  The STAT3 inhibitor NSC 74859 is effective in hepatocellular cancers with disrupted TGF-β signaling , 2009, Oncogene.

[6]  Yue Chen,et al.  Sex-modified effect of hepatitis B virus infection on mortality from primary liver cancer. , 2009, American journal of epidemiology.

[7]  K. N. Chandrika,et al.  Analysis of the human protein interactome and comparison with yeast, worm and fly interaction datasets , 2006, Nature Genetics.

[8]  Bernard F. Buxton,et al.  The DISOPRED server for the prediction of protein disorder , 2004, Bioinform..

[9]  J. Dopazo,et al.  Evidence for systems-level molecular mechanisms of tumorigenesis , 2007, BMC Genomics.

[10]  Christian von Mering,et al.  STRING: known and predicted protein–protein associations, integrated and transferred across organisms , 2004, Nucleic Acids Res..

[11]  M. Vidal,et al.  Hepatitis C virus infection protein network , 2008, Molecular systems biology.

[12]  N. Xu,et al.  Toll-like receptor 7 and 9 expression in peripheral blood mononuclear cells from patients with chronic hepatitis B and related hepatocellular carcinoma , 2008, Acta Pharmacologica Sinica.

[13]  Douglas A. Hosack,et al.  Identifying biological themes within lists of genes with EASE , 2003, Genome Biology.

[14]  S. Bontron,et al.  Hepatitis B Virus X Protein Stimulates Viral Genome Replication via a DDB1-Dependent Pathway Distinct from That Leading to Cell Death , 2005, Journal of Virology.

[15]  S. Wilhelm,et al.  Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5. , 2006, Cancer research.

[16]  Ding-Shinn Chen,et al.  Global control of hepatitis B virus infection. , 2002, The Lancet. Infectious diseases.

[17]  Wan-Wan Lin,et al.  Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis , 2009, Nature.

[18]  Rongxi Yang,et al.  Rapid xenograft tumor progression in beta‐arrestin1 transgenic mice due to enhanced tumor angiogenesis , 2008, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[19]  Y. Benjamini,et al.  Controlling the false discovery rate in behavior genetics research , 2001, Behavioural Brain Research.

[20]  N. Park,et al.  Chronic hepatitis B in hepatocarcinogenesis , 2006, Postgraduate Medical Journal.

[21]  Dietrich Rebholz-Schuhmann,et al.  Text processing through Web services: calling Whatizit , 2008, Bioinform..

[22]  I. Fabregat.  Dysregulation of apoptosis in hepatocellular carcinoma cells. , 2009, World journal of gastroenterology.

[23]  Soon-Heng Tan,et al.  Functional centrality: detecting lethality of proteins in protein interaction networks. , 2007, Genome informatics. International Conference on Genome Informatics.

[24]  S. Volinia,et al.  Gene Expression Analysis in HBV Transgenic Mouse Liver: A Model to Study Early Events Related to Hepatocarcinogenesis , 2006, Molecular medicine.

[25]  C. Harris,et al.  TP53 mutations and hepatocellular carcinoma: insights into the etiology and pathogenesis of liver cancer , 2007, Oncogene.

[26]  A. Vazquez,et al.  Epstein–Barr virus and virus human protein interaction maps , 2007, Proceedings of the National Academy of Sciences.

[27]  A. Filippini,et al.  Toll-like receptor 3 triggers apoptosis of human prostate cancer cells through a PKC-alpha-dependent mechanism. , 2008, Carcinogenesis.

[28]  A. Semczuk,et al.  Alterations of pRb1-cyclin D1-cdk4/6-p16(INK4A) pathway in endometrial carcinogenesis. , 2004, Cancer letters.

[29]  K. Matsuzaki.  Modulation of TGF-beta signaling during progression of chronic liver diseases. , 2009, Frontiers in bioscience.

[30]  M. DePamphilis,et al.  HUMAN DISEASE , 1957, The Ulster Medical Journal.

[31]  B. Cuevas,et al.  Persistent transactivation of EGFR and ErbB2/HER2 by protease-activated receptor-1 promotes breast carcinoma cell invasion , 2008, Oncogene.

[32]  Q. He,et al.  Regulation of focal adhesion turnover by ErbB signalling in invasive breast cancer cells , 2009, British Journal of Cancer.

[33]  Matthew D. Dyer,et al.  The Landscape of Human Proteins Interacting with Viruses and Other Pathogens , 2008, PLoS pathogens.

[34]  Michael Ashburner,et al.  On ontologies for biologists: the Gene Ontology--untangling the web. , 2002, Novartis Foundation symposium.

[35]  Yoshihiro Yamanishi,et al.  KEGG for linking genomes to life and the environment , 2007, Nucleic Acids Res..

[36]  I. Fabregat,et al.  Survival and apoptosis: a dysregulated balance in liver cancer , 2007, Liver international : official journal of the International Association for the Study of the Liver.

[37]  Peer Bork,et al.  Medusa: a simple tool for interaction graph analysis , 2005, Bioinform..

[38]  M. Ronaghi,et al.  Deregulated Direct Targets of the Hepatitis B Virus (HBV) Protein, HBx, Identified through Chromatin Immunoprecipitation and Expression Microarray Profiling* , 2009, The Journal of Biological Chemistry.

[39]  Burr Settles,et al.  ABNER: an open source tool for automatically tagging genes, proteins and other entity names in text , 2005 .

[40]  M. Strubin,et al.  Hepatitis B virus X protein affects S phase progression leading to chromosome segregation defects by binding to damaged DNA binding protein 1 , 2008, Hepatology.

[41]  A. Barabasi,et al.  The human disease network , 2007, Proceedings of the National Academy of Sciences.