File Download
 
Links for fulltext
(May Require Subscription)
 
Supplementary

Article: Carboxyl-terminal truncated HBx regulates a distinct microRNA transcription program in Hepatocellular carcinoma development
  • Basic View
  • Metadata View
  • XML View
TitleCarboxyl-terminal truncated HBx regulates a distinct microRNA transcription program in Hepatocellular carcinoma development
 
AuthorsYip, WK2
Cheng, ASL2
Zhu, R2
Lung, RWM2
Tsang, DPF2
Lau, SSK2
Chen, Y2
Sung, JG2
Lai, PBS2
Ng, EKO2 1
Yu, J2
Wong, N2
To, KF2
Wong, VWS2
Sung, JJY2
Chan, HLY2
 
Issue Date2011
 
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
 
CitationPlos One, 2011, v. 6 n. 8 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pone.0022888
 
AbstractBackground: The biological pathways and functional properties by which misexpressed microRNAs (miRNAs) contribute to liver carcinogenesis have been intensively investigated. However, little is known about the upstream mechanisms that deregulate miRNA expressions in this process. In hepatocellular carcinoma (HCC), hepatitis B virus (HBV) X protein (HBx), a transcriptional trans-activator, is frequently expressed in truncated form without carboxyl-terminus but its role in miRNA expression and HCC development is unclear. Methods: Human non-tumorigenic hepatocytes were infected with lentivirus-expressing full-length and carboxyl-terminal truncated HBx (Ct-HBx) for cell growth assay and miRNA profiling. Chromatin immunoprecipitation microarray was performed to identify the miRNA promoters directly associated with HBx. Direct transcriptional control was verified by luciferase reporter assay. The differential miRNA expressions were further validated in a cohort of HBV-associated HCC tissues using real-time PCR. Results: Hepatocytes expressing Ct-HBx grew significantly faster than the full-length HBx counterparts. Ct-HBx decreased while full-length HBx increased the expression of a set of miRNAs with growth-suppressive functions. Interestingly, Ct-HBx bound to and inhibited the transcriptional activity of some of these miRNA promoters. Notably, some of the examined repressed-miRNAs (miR-26a, -29c, -146a and -190) were also significantly down-regulated in a subset of HCC tissues with carboxyl-terminal HBx truncation compared to their matching non-tumor tissues, highlighting the clinical relevance of our data. Conclusion: Our results suggest that Ct-HBx directly regulates miRNA transcription and in turn promotes hepatocellular proliferation, thus revealing a viral contribution of miRNA deregulation during hepatocarcinogenesis. © 2011 Yip et al.
 
ISSN1932-6203
2013 Impact Factor: 3.534
2013 SCImago Journal Rankings: 1.724
 
DOIhttp://dx.doi.org/10.1371/journal.pone.0022888
 
PubMed Central IDPMC3150371
 
ISI Accession Number IDWOS:000293561200034
Funding AgencyGrant Number
Hong Kong Government08070332
09080042
Research Grants Council09/060/GRF
462309
Collaborative Research FundCUHK04/CRF/08
Funding Information:

This work was supported by grants from the Hong Kong Government Research Fund for the Control of Infectious Diseases (08070332) to AS-LC, JJ-YS and HL-YC; (09080042) to AS-LC and JJ-YS; from the Research Grants Council General Research Fund (09/060/GRF and 462309) to AS-LC and JJ-YS; and from the Collaborative Research Fund (CUHK04/CRF/08) to AS-LC, NW and K-FT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorYip, WK
 
dc.contributor.authorCheng, ASL
 
dc.contributor.authorZhu, R
 
dc.contributor.authorLung, RWM
 
dc.contributor.authorTsang, DPF
 
dc.contributor.authorLau, SSK
 
dc.contributor.authorChen, Y
 
dc.contributor.authorSung, JG
 
dc.contributor.authorLai, PBS
 
dc.contributor.authorNg, EKO
 
dc.contributor.authorYu, J
 
dc.contributor.authorWong, N
 
dc.contributor.authorTo, KF
 
dc.contributor.authorWong, VWS
 
dc.contributor.authorSung, JJY
 
dc.contributor.authorChan, HLY
 
dc.date.accessioned2012-02-03T06:15:12Z
 
dc.date.available2012-02-03T06:15:12Z
 
dc.date.issued2011
 
dc.description.abstractBackground: The biological pathways and functional properties by which misexpressed microRNAs (miRNAs) contribute to liver carcinogenesis have been intensively investigated. However, little is known about the upstream mechanisms that deregulate miRNA expressions in this process. In hepatocellular carcinoma (HCC), hepatitis B virus (HBV) X protein (HBx), a transcriptional trans-activator, is frequently expressed in truncated form without carboxyl-terminus but its role in miRNA expression and HCC development is unclear. Methods: Human non-tumorigenic hepatocytes were infected with lentivirus-expressing full-length and carboxyl-terminal truncated HBx (Ct-HBx) for cell growth assay and miRNA profiling. Chromatin immunoprecipitation microarray was performed to identify the miRNA promoters directly associated with HBx. Direct transcriptional control was verified by luciferase reporter assay. The differential miRNA expressions were further validated in a cohort of HBV-associated HCC tissues using real-time PCR. Results: Hepatocytes expressing Ct-HBx grew significantly faster than the full-length HBx counterparts. Ct-HBx decreased while full-length HBx increased the expression of a set of miRNAs with growth-suppressive functions. Interestingly, Ct-HBx bound to and inhibited the transcriptional activity of some of these miRNA promoters. Notably, some of the examined repressed-miRNAs (miR-26a, -29c, -146a and -190) were also significantly down-regulated in a subset of HCC tissues with carboxyl-terminal HBx truncation compared to their matching non-tumor tissues, highlighting the clinical relevance of our data. Conclusion: Our results suggest that Ct-HBx directly regulates miRNA transcription and in turn promotes hepatocellular proliferation, thus revealing a viral contribution of miRNA deregulation during hepatocarcinogenesis. © 2011 Yip et al.
 
dc.description.naturepublished_or_final_version
 
dc.identifier.citationPlos One, 2011, v. 6 n. 8 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pone.0022888
 
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0022888
 
dc.identifier.epagee22888
 
dc.identifier.hkuros198393
 
dc.identifier.isiWOS:000293561200034
Funding AgencyGrant Number
Hong Kong Government08070332
09080042
Research Grants Council09/060/GRF
462309
Collaborative Research FundCUHK04/CRF/08
Funding Information:

This work was supported by grants from the Hong Kong Government Research Fund for the Control of Infectious Diseases (08070332) to AS-LC, JJ-YS and HL-YC; (09080042) to AS-LC and JJ-YS; from the Research Grants Council General Research Fund (09/060/GRF and 462309) to AS-LC and JJ-YS; and from the Collaborative Research Fund (CUHK04/CRF/08) to AS-LC, NW and K-FT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

 
dc.identifier.issn1932-6203
2013 Impact Factor: 3.534
2013 SCImago Journal Rankings: 1.724
 
dc.identifier.issue8
 
dc.identifier.pmcidPMC3150371
 
dc.identifier.pmid21829663
 
dc.identifier.scopuseid_2-s2.0-79961136142
 
dc.identifier.spagee22888
 
dc.identifier.urihttp://hdl.handle.net/10722/144600
 
dc.identifier.volume6
 
dc.languageeng
 
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
 
dc.publisher.placeUnited States
 
dc.relation.ispartofPLoS ONE
 
dc.relation.referencesReferences in Scopus
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.subject.meshCarcinoma, Hepatocellular - genetics - pathology
 
dc.subject.meshCell Transformation, Neoplastic
 
dc.subject.meshLiver Neoplasms - genetics - pathology
 
dc.subject.meshMicroRNAs - genetics
 
dc.subject.meshTrans-Activators - chemistry - genetics - physiology
 
dc.titleCarboxyl-terminal truncated HBx regulates a distinct microRNA transcription program in Hepatocellular carcinoma development
 
dc.typeArticle
 
<?xml encoding="utf-8" version="1.0"?>
<item><contributor.author>Yip, WK</contributor.author>
<contributor.author>Cheng, ASL</contributor.author>
<contributor.author>Zhu, R</contributor.author>
<contributor.author>Lung, RWM</contributor.author>
<contributor.author>Tsang, DPF</contributor.author>
<contributor.author>Lau, SSK</contributor.author>
<contributor.author>Chen, Y</contributor.author>
<contributor.author>Sung, JG</contributor.author>
<contributor.author>Lai, PBS</contributor.author>
<contributor.author>Ng, EKO</contributor.author>
<contributor.author>Yu, J</contributor.author>
<contributor.author>Wong, N</contributor.author>
<contributor.author>To, KF</contributor.author>
<contributor.author>Wong, VWS</contributor.author>
<contributor.author>Sung, JJY</contributor.author>
<contributor.author>Chan, HLY</contributor.author>
<date.accessioned>2012-02-03T06:15:12Z</date.accessioned>
<date.available>2012-02-03T06:15:12Z</date.available>
<date.issued>2011</date.issued>
<identifier.citation>Plos One, 2011, v. 6 n. 8</identifier.citation>
<identifier.issn>1932-6203</identifier.issn>
<identifier.uri>http://hdl.handle.net/10722/144600</identifier.uri>
<description.abstract>Background: The biological pathways and functional properties by which misexpressed microRNAs (miRNAs) contribute to liver carcinogenesis have been intensively investigated. However, little is known about the upstream mechanisms that deregulate miRNA expressions in this process. In hepatocellular carcinoma (HCC), hepatitis B virus (HBV) X protein (HBx), a transcriptional trans-activator, is frequently expressed in truncated form without carboxyl-terminus but its role in miRNA expression and HCC development is unclear. Methods: Human non-tumorigenic hepatocytes were infected with lentivirus-expressing full-length and carboxyl-terminal truncated HBx (Ct-HBx) for cell growth assay and miRNA profiling. Chromatin immunoprecipitation microarray was performed to identify the miRNA promoters directly associated with HBx. Direct transcriptional control was verified by luciferase reporter assay. The differential miRNA expressions were further validated in a cohort of HBV-associated HCC tissues using real-time PCR. Results: Hepatocytes expressing Ct-HBx grew significantly faster than the full-length HBx counterparts. Ct-HBx decreased while full-length HBx increased the expression of a set of miRNAs with growth-suppressive functions. Interestingly, Ct-HBx bound to and inhibited the transcriptional activity of some of these miRNA promoters. Notably, some of the examined repressed-miRNAs (miR-26a, -29c, -146a and -190) were also significantly down-regulated in a subset of HCC tissues with carboxyl-terminal HBx truncation compared to their matching non-tumor tissues, highlighting the clinical relevance of our data. Conclusion: Our results suggest that Ct-HBx directly regulates miRNA transcription and in turn promotes hepatocellular proliferation, thus revealing a viral contribution of miRNA deregulation during hepatocarcinogenesis. &#169; 2011 Yip et al.</description.abstract>
<language>eng</language>
<publisher>Public Library of Science. The Journal&apos;s web site is located at http://www.plosone.org/home.action</publisher>
<relation.ispartof>PLoS ONE</relation.ispartof>
<rights>Creative Commons: Attribution 3.0 Hong Kong License</rights>
<subject.mesh>Carcinoma, Hepatocellular - genetics - pathology</subject.mesh>
<subject.mesh>Cell Transformation, Neoplastic</subject.mesh>
<subject.mesh>Liver Neoplasms - genetics - pathology</subject.mesh>
<subject.mesh>MicroRNAs - genetics</subject.mesh>
<subject.mesh>Trans-Activators - chemistry - genetics - physiology</subject.mesh>
<title>Carboxyl-terminal truncated HBx regulates a distinct microRNA transcription program in Hepatocellular carcinoma development</title>
<type>Article</type>
<description.nature>published_or_final_version</description.nature>
<identifier.doi>10.1371/journal.pone.0022888</identifier.doi>
<identifier.pmid>21829663</identifier.pmid>
<identifier.pmcid>PMC3150371</identifier.pmcid>
<identifier.scopus>eid_2-s2.0-79961136142</identifier.scopus>
<identifier.hkuros>198393</identifier.hkuros>
<relation.references>http://www.scopus.com/mlt/select.url?eid=2-s2.0-79961136142&amp;selection=ref&amp;src=s&amp;origin=recordpage</relation.references>
<identifier.volume>6</identifier.volume>
<identifier.issue>8</identifier.issue>
<identifier.spage>e22888</identifier.spage>
<identifier.epage>e22888</identifier.epage>
<identifier.isi>WOS:000293561200034</identifier.isi>
<publisher.place>United States</publisher.place>
<bitstream.url>http://hub.hku.hk/bitstream/10722/144600/1/pone.0022888.pdf</bitstream.url>
</item>
Author Affiliations
  1. The University of Hong Kong
  2. Chinese University of Hong Kong