1887

Abstract

Both isoforms of the hepatitis delta antigen (HDAg) of hepatitis delta virus (HDV) are highly associated with virus proliferation and may act as co-activators of cellular gene expression. Human hepatocellular carcinoma (HCC) cell line Huh7, which stably expresses HDAgs, was differentially screened and the results showed that clusterin gene expression was enhanced. The mechanisms for HDAg-mediated clusterin gene upregulation were investigated. Expression of HDAgs was associated with enhanced histone H3 acetylation within the clusterin promoter in a chromatin immunoprecipitation assay. Transient transfection of HDAg-expressing plasmids into Huh7 cells also enhanced clusterin expression and histone acetylation. Furthermore, HDV replication was associated with histone hyperacetylation and clusterin induction. The effect of increased clusterin expression was determined by a chemosensitivity assay with adriamycin treatment. These data indicated that HDV-induced clusterin protein increases cell survival potential. Thus, it is possible that epigenetic regulation by HDV contributes to a pathological outcome of hepatitis D/hepatitis B viral hepatitis and HCC.

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2009-05-01
2019-11-14
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References

  1. Aden, D. P., Fogel, A., Plotkin, S., Damjanov, I. & Knowles, B. B. ( 1979; ). Controlled synthesis of HBsAg in a differentiated human liver carcinoma-derived cell line. Nature 282, 615–616.[CrossRef]
    [Google Scholar]
  2. Blaschuk, O., Burdzy, K. & Fritz, I. B. ( 1983; ). Purification and characterization of a cell-aggregating factor (clusterin), the major glycoprotein in ram rete testis fluid. J Biol Chem 258, 7714–7720.
    [Google Scholar]
  3. Bonino, F., Heermann, K. H., Rizzetto, M. & Gerlich, W. H. ( 1986; ). Hepatitis delta virus: protein composition of delta antigen and its hepatitis B virus-derived envelope. J Virol 58, 945–950.
    [Google Scholar]
  4. Brehm, A., Nielsen, S. J., Miska, E. A., McCance, D. J., Reid, J. L., Bannister, A. J. & Kouzarides, T. ( 1999; ). The E7 oncoprotein associates with Mi2 and histone deacetylase activity to promote cell growth. EMBO J 18, 2449–2458.[CrossRef]
    [Google Scholar]
  5. Buti, M., Estebán, R., Jardi, R., Allende, H., Estebán, J. I., Genesca, J. & Guardia, J. ( 1987; ). Clinical and serological outcome of acute delta infection. J Hepatol 5, 59–64.[CrossRef]
    [Google Scholar]
  6. Chakravarti, D., Ogryzko, V., Kao, H. Y., Nash, A., Chen, H., Nakatani, Y. & Evans, R. M. ( 1999; ). A viral mechanism for inhibition of p300 and PCAF acetyltransferase activity. Cell 96, 393–403.[CrossRef]
    [Google Scholar]
  7. Chang, F. L., Chen, P. J., Tu, S. J., Wang, C. J. & Chen, D. S. ( 1991; ). The large form of hepatitis delta antigen is crucial for assembly of hepatitis delta virus. Proc Natl Acad Sci U S A 88, 8490–8494.[CrossRef]
    [Google Scholar]
  8. Chang, J. T., Chang, G. C., Ko, J. L., Liao, H. Y., Liu, H. J., Chen, C. C., Su, J. M., Lee, H. & Sheu, G. T. ( 2006; ). Induction of tubulin by docetaxel is associated with p53 status in human non small cell lung cancer cell lines. Int J Cancer 118, 317–325.[CrossRef]
    [Google Scholar]
  9. Choi, S. H., Jeong, S. H. & Hwang, S. B. ( 2007; ). Large hepatitis delta antigen modulates transforming growth factor-β signaling cascades: implication of hepatitis delta virus-induced liver fibrosis. Gastroenterology 132, 343–357.[CrossRef]
    [Google Scholar]
  10. Choi-Miura, N. H., Takahashi, Y., Nakano, Y., Tobe, T. & Tomita, M. ( 1992; ). Identification of the disulfide bonds in human plasma protein SP-40,40 (apolipoprotein-J). J Biochem 112, 557–561.
    [Google Scholar]
  11. Colombo, M., Cambieri, R., Rumi, M. G., Ronchi, G., Del Ninno, E. & De Franchis, R. ( 1983; ). Long-term delta superinfection in hepatitis B surface antigen carriers and its relationship to the course of chronic hepatitis. Gastroenterology 85, 235–239.
    [Google Scholar]
  12. Criswell, T., Klokov, D., Beman, M., Lavik, J. P. & Boothman, D. A. ( 2003; ). Repression of IR-inducible clusterin expression by the p53 tumor suppressor protein. Cancer Biol Ther 2, 372–380.[CrossRef]
    [Google Scholar]
  13. Fattovich, G., Boscaro, S., Noventa, F., Pornaro, E., Stenico, D., Alberti, A., Ruol, A. & Realdi, G. ( 1987; ). Influence of hepatitis delta virus infection on progression to cirrhosis in chronic hepatitis type B. J Infect Dis 155, 931–935.[CrossRef]
    [Google Scholar]
  14. Feng, J. T., Liu, Y. K., Song, H. Y., Dai, Z., Qin, L. X., Almofti, M. R., Fang, C. Y., Lu, H. J., Yang, P. Y. & Tang, Z. Y. ( 2005; ). Heat-shock protein 27: a potential biomarker for hepatocellular carcinoma identified by serum proteome analysis. Proteomics 5, 4581–4588.[CrossRef]
    [Google Scholar]
  15. Goto, T., Kato, N., Ono-Nita, S. K., Yoshida, H., Otsuka, M., Shiratori, Y. & Omata, M. ( 2000; ). Large isoform of hepatitis delta antigen activates serum response factor-associated transcription. J Biol Chem 275, 37311–37316.[CrossRef]
    [Google Scholar]
  16. Gray, S. G. & Teh, B. T. ( 2001; ). Histone acetylation/deacetylation and cancer: an “open” and “shut” case? Curr Mol Med 1, 401–429.[CrossRef]
    [Google Scholar]
  17. Hamamori, Y., Sartorelli, V., Ogryzko, V., Puri, P. L., Wu, H. Y., Wang, J. Y., Nakatani, Y. & Kedes, L. ( 1999; ). Regulation of histone acetyltransferases p300 and PCAF by the bHLH protein twist and adenoviral oncoprotein E1A. Cell 96, 405–413.[CrossRef]
    [Google Scholar]
  18. Huang, W. H., Yung, B. Y., Syu, W. J. & Lee, Y. H. ( 2001; ). The nucleolar phosphoprotein B23 interacts with hepatitis delta antigens and modulates the hepatitis delta virus RNA replication. J Biol Chem 276, 25166–25175.[CrossRef]
    [Google Scholar]
  19. Huang, W. H., Mai, R. T. & Lee, Y. H. ( 2008; ). Transcription factor YY1 and its associated acetyltransferases CBP and p300 interact with hepatitis delta antigens and modulate hepatitis delta virus RNA replication. J Virol 82, 7313–7324.[CrossRef]
    [Google Scholar]
  20. Kang, Y. K., Hong, S. W., Lee, H. & Kim, W. H. ( 2004; ). Overexpression of clusterin in human hepatocellular carcinoma. Hum Pathol 35, 1340–1346.[CrossRef]
    [Google Scholar]
  21. Kim, Y. J., Kwak, C. I., Gu, Y. Y., Hwang, I. T. & Chun, J. Y. ( 2004; ). Annealing control primer system for identification of differentially expressed genes on agarose gels. Biotechniques 36, 424–426, 428, 430 passim.
    [Google Scholar]
  22. Lau, S. H., Sham, J. S., Xie, D., Tzang, C. H., Tang, D., Ma, N., Hu, L., Wang, Y., Wen, J. M. & other authors ( 2006; ). Clusterin plays an important role in hepatocellular carcinoma metastasis. Oncogene 25, 1242–1250.[CrossRef]
    [Google Scholar]
  23. Lee, C. Z. & Sheu, J. C. ( 2008; ). Histone H1e interacts with small hepatitis delta antigen and affects hepatitis delta virus replication. Virology 375, 197–204.[CrossRef]
    [Google Scholar]
  24. Leskov, K. S., Klokov, D. Y., Li, J., Kinsella, T. J. & Boothman, D. A. ( 2003; ). Synthesis and functional analyses of nuclear clusterin, a cell death protein. J Biol Chem 278, 11590–11600.[CrossRef]
    [Google Scholar]
  25. Loison, F., Debure, L., Nizard, P., le Goff, P., Michel, D. & le Dréan, Y. ( 2006; ). Up-regulation of the clusterin gene after proteotoxic stress: implication of HSF1–HSF2 heterocomplexes. Biochem J 395, 223–231.[CrossRef]
    [Google Scholar]
  26. Lund, P., Weisshaupt, K., Mikeska, T., Jammas, D., Chen, X., Kuban, R. J., Ungethüm, U., Krapfenbauer, U., Herzel, H. P. & other authors ( 2006; ). Oncogenic HRAS suppresses clusterin expression through promoter hypermethylation. Oncogene 25, 4890–4903.[CrossRef]
    [Google Scholar]
  27. Michel, D., Chatelain, G., North, S. & Brun, G. ( 1997; ). Stress-induced transcription of the clusterinapoJ gene. Biochem J 328, 45–50.
    [Google Scholar]
  28. Miyake, H., Hara, I., Fujisawa, M. & Gleave, M. E. ( 2006; ). The potential of clusterin inhibiting antisense oligodeoxynucleotide therapy for prostate cancer. Expert Opin Investig Drugs 15, 507–517.[CrossRef]
    [Google Scholar]
  29. Nuutinen, T., Suuronen, T., Kyrylenko, S., Huuskonen, J. & Salminen, A. ( 2005; ). Induction of clusterin/apoJ expression by histone deacetylase inhibitors in neural cells. Neurochem Int 47, 528–538.[CrossRef]
    [Google Scholar]
  30. Oliveri, F., Brunetto, M. R., Actis, G. C. & Bonino, F. ( 1991; ). Pathobiology of chronic hepatitis virus infection and hepatocellular carcinoma (HCC). Ital J Gastroenterol 23, 498–502.
    [Google Scholar]
  31. Polson, A. G., Bass, B. L. & Casey, J. L. ( 1996; ). RNA editing of hepatitis delta virus antigenome by dsRNA-adenosine deaminase. Nature 380, 454–456.[CrossRef]
    [Google Scholar]
  32. Rizzetto, M., Shih, J. W., Gocke, D. J., Purcell, R. H., Verme, G. & Gerin, J. L. ( 1979; ). Incidence and significance of antibodies to delta antigen in hepatitis B virus infection. Lancet 2, 986–990.
    [Google Scholar]
  33. Sheu, G. T. ( 2002; ). Initiation of hepatitis delta virus (HDV) replication: HDV RNA encoding the large delta antigen cannot replicate. J Gen Virol 83, 2507–2513.
    [Google Scholar]
  34. Sheu, G. T. & Lai, M. M. ( 2000; ). Recombinant hepatitis delta antigen from E. coli promotes hepatitis delta virus RNA replication only from the genomic strand but not the antigenomic strand. Virology 278, 578–586.[CrossRef]
    [Google Scholar]
  35. Smedile, A., Farci, P., Verme, G., Caredda, F., Cargnel, A., Caporaso, N., Dentico, P., Trepo, C., Opolon, P. & other authors ( 1982; ). Influence of delta infection on severity of hepatitis B. Lancet 2, 945–947.
    [Google Scholar]
  36. Trougakos, I. P. & Gonos, E. S. ( 2002; ). Clusterin/apolipoprotein J in human aging and cancer. Int J Biochem Cell Biol 34, 1430–1448.[CrossRef]
    [Google Scholar]
  37. Trougakos, I. P. & Gonos, E. S. ( 2006; ). Regulation of clusterin/apolipoprotein J, a functional homologue to the small heat shock proteins, by oxidative stress in ageing and age-related diseases. Free Radic Res 40, 1324–1334.[CrossRef]
    [Google Scholar]
  38. Valls, E., de la Cruz, X. & Martínez-Balbás, M. A. ( 2003; ). The SV40 T antigen modulates CBP histone acetyltransferase activity. Nucleic Acids Res 31, 3114–3122.[CrossRef]
    [Google Scholar]
  39. Verme, G., Brunetto, M. R., Oliveri, F., Baldi, M., Forzani, B., Piantino, P., Ponzetto, A. & Bonino, F. ( 1991; ). Role of hepatitis delta virus infection in hepatocellular carcinoma. Dig Dis Sci 36, 1134–1136.[CrossRef]
    [Google Scholar]
  40. Waris, G. & Siddiqui, A. ( 2003; ). Regulatory mechanisms of viral hepatitis B and C. J Biosci 28, 311–321.[CrossRef]
    [Google Scholar]
  41. Wei, Y. & Ganem, D. ( 1998; ). Activation of heterologous gene expression by the large isoform of hepatitis delta antigen. J Virol 72, 2089–2096.
    [Google Scholar]
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