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Article: C-terminal truncated hepatitis B virus x protein is associated with metastasis and enhances invasiveness by C-Jun/matrix metalloproteinase protein 10 activation in hepatocellular carcinoma

TitleC-terminal truncated hepatitis B virus x protein is associated with metastasis and enhances invasiveness by C-Jun/matrix metalloproteinase protein 10 activation in hepatocellular carcinoma
Authors
Issue Date2013
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/
Citation
Hepatology, 2013, v. 57 n. 1, p. 131-139 How to Cite?
AbstractRandom integration of hepatitis B virus (HBV) DNA into the host genome is frequent in human hepatocellular carcinoma (HCC) and this leads to truncation of the HBV DNA, particularly at the C-terminal end of the HBV X protein (HBx). In this study, we investigated the frequency of this natural C-terminal truncation of HBx in human HCCs and its functional significance. In 50 HBV-positive patients with HCC, full-length HBx was detected in all nontumorous livers. However, full-length HBx was found in only 27 (54%) of the HCC tumors, whereas natural carboxylic acid (COOH)-truncated HBx was found in the remaining 23 (46%) tumors. Upon clinicopathological analysis, the presence of natural COOH-truncated HBx significantly correlated with the presence of venous invasion, a hallmark of metastasis (P = 0.005). Inducible stable expression of the COOH-truncated HBx protein (with 24 amino acids truncated at the C-terminal end) enhanced the cell-invasive ability of HepG2 cells, as compared to full-length HBx, using the Matrigel cell-invasion assay. It also resulted in increased C-Jun transcriptional activity and enhanced transcription of matrix metalloproteinase 10 (MMP10), whereas activation of the MMP10 promoter by COOH-truncated HBx was abolished when the activator protein 1-binding sites on the MMP10 promoter were mutated. Furthermore, silencing of MMP10 by short interfering RNA in HBxDeltaC1-expressing HepG2 cells resulted in significant reduction of cell invasiveness. CONCLUSIONS: Our data suggest that COOH truncation of HBx, particularly with 24 amino acids truncated at the C-terminal end, plays a role in enhancing cell invasiveness and metastasis in HCC by activating MMP10 through C-Jun.
Persistent Identifierhttp://hdl.handle.net/10722/160059
ISSN
2015 Impact Factor: 11.711
2015 SCImago Journal Rankings: 4.752
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorSze, MFen_US
dc.contributor.authorChu, KYen_US
dc.contributor.authorLee, MFen_US
dc.contributor.authorNg, IOLen_US
dc.date.accessioned2012-08-16T06:02:09Z-
dc.date.available2012-08-16T06:02:09Z-
dc.date.issued2013en_US
dc.identifier.citationHepatology, 2013, v. 57 n. 1, p. 131-139en_US
dc.identifier.issn0270-9139en_US
dc.identifier.urihttp://hdl.handle.net/10722/160059-
dc.description.abstractRandom integration of hepatitis B virus (HBV) DNA into the host genome is frequent in human hepatocellular carcinoma (HCC) and this leads to truncation of the HBV DNA, particularly at the C-terminal end of the HBV X protein (HBx). In this study, we investigated the frequency of this natural C-terminal truncation of HBx in human HCCs and its functional significance. In 50 HBV-positive patients with HCC, full-length HBx was detected in all nontumorous livers. However, full-length HBx was found in only 27 (54%) of the HCC tumors, whereas natural carboxylic acid (COOH)-truncated HBx was found in the remaining 23 (46%) tumors. Upon clinicopathological analysis, the presence of natural COOH-truncated HBx significantly correlated with the presence of venous invasion, a hallmark of metastasis (P = 0.005). Inducible stable expression of the COOH-truncated HBx protein (with 24 amino acids truncated at the C-terminal end) enhanced the cell-invasive ability of HepG2 cells, as compared to full-length HBx, using the Matrigel cell-invasion assay. It also resulted in increased C-Jun transcriptional activity and enhanced transcription of matrix metalloproteinase 10 (MMP10), whereas activation of the MMP10 promoter by COOH-truncated HBx was abolished when the activator protein 1-binding sites on the MMP10 promoter were mutated. Furthermore, silencing of MMP10 by short interfering RNA in HBxDeltaC1-expressing HepG2 cells resulted in significant reduction of cell invasiveness. CONCLUSIONS: Our data suggest that COOH truncation of HBx, particularly with 24 amino acids truncated at the C-terminal end, plays a role in enhancing cell invasiveness and metastasis in HCC by activating MMP10 through C-Jun.-
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/-
dc.relation.ispartofHepatologyen_US
dc.rightsHepatology. Copyright © John Wiley & Sons, Inc.-
dc.rightsSpecial Statement for Preprint only Before publication: 'This is a preprint of an article accepted for publication in [The Journal of Pathology] Copyright © ([year]) ([Pathological Society of Great Britain and Ireland])'. After publication: the preprint notice should be amended to follows: 'This is a preprint of an article published in [include the complete citation information for the final version of the Contribution as published in the print edition of the Journal]' For Cochrane Library/ Cochrane Database of Systematic Reviews, add statement & acknowledgement : ‘This review is published as a Cochrane Review in the Cochrane Database of Systematic Reviews 20XX, Issue X. Cochrane Reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and the Cochrane Database of Systematic Reviews should be consulted for the most recent version of the Review.’ Please include reference to the Review and hyperlink to the original version using the following format e.g. Authors. Title of Review. Cochrane Database of Systematic Reviews 20XX, Issue #. Art. No.: CD00XXXX. DOI: 10.1002/14651858.CD00XXXX (insert persistent link to the article by using the URL: http://dx.doi.org/10.1002/14651858.CD00XXXX) (This statement should refer to the most recent issue of the Cochrane Database of Systematic Reviews in which the Review published.)-
dc.subject.meshCarcinoma, Hepatocellular - enzymology - pathology - virology-
dc.subject.meshJNK Mitogen-Activated Protein Kinases - metabolism-
dc.subject.meshLiver Neoplasms - enzymology - pathology - virology-
dc.subject.meshMatrix Metalloproteinase 10 - metabolism-
dc.subject.meshTrans-Activators - metabolism-
dc.titleC-terminal truncated hepatitis B virus x protein is associated with metastasis and enhances invasiveness by C-Jun/matrix metalloproteinase protein 10 activation in hepatocellular carcinomaen_US
dc.typeArticleen_US
dc.identifier.emailSze, MF: karensze@hkucc.hku.hken_US
dc.identifier.emailChu, KY: glanice@hku.hken_US
dc.identifier.emailLee, MF: joyce@pathology.hku.hken_US
dc.identifier.emailNg, IOL: iolng@hku.hken_US
dc.identifier.doi10.1002/hep.25979-
dc.identifier.pmid22821423-
dc.identifier.hkuros204787en_US
dc.identifier.volume57-
dc.identifier.issue1-
dc.identifier.spage131-
dc.identifier.epage139-
dc.identifier.isiWOS:000313547700016-
dc.publisher.placeUnited States-

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