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Article: MicroRNA silencing of tumor suppressor DLC-1 promotes efficient hepatitis C virus replication in primary human hepatocytes

TitleMicroRNA silencing of tumor suppressor DLC-1 promotes efficient hepatitis C virus replication in primary human hepatocytes
Authors
Issue Date2011
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/
Citation
Hepatology, 2011, v. 53 n. 1, p. 53-61 How to Cite?
AbstractMicroRNAs (miRNAs) are approximately 22-nucleotide noncoding RNAs that constitute silencers of target gene expression. Aberrant expression of miRNA has been linked to a variety of cancers, including hepatocellular carcinoma (HCC). Hepatitis C virus (HCV) infection is considered a major cause of chronic liver disease and HCC, although the mechanism of virus infection-associated hepatocarcinogenesis remains unclear. We report a direct role of miRNAs induced in HCV-infected primary human hepatocytes that target the tumor suppressor gene DLC-1 (a Rho GTPase-activating protein), which is frequently deleted in HCC, and other solid human tumors. MicroRNA miR-141 that targets DLC-1 was accentuated in cells infected with HCV genotypes 1a, 1b, and 2a. We present several lines of evidence that efficient HCV replication requires miR-141-mediated suppression of DLC-1. An increase in miR-141 correlated with the inhibition of DLC-1 protein in HCV-infected cells. Depletion of miR-141 with oligonucleotides complementary to the miRNAs inhibited virus replication, whereas artificially increased levels of intracellular miR-141 enhanced HCV replication. HCV-infected hepatocytes showed enhanced cell proliferation that can be countered by overexpression of DLC-1. Conclusion: The collective results of this study suggest a novel mechanism of HCV infection-associated miRNA-mediated regulation of a tumor suppressor protein that has the ability to influence cell proliferation and HCV infection-mediated liver cancer. © 2010 American Association for the Study of Liver Diseases.
Persistent Identifierhttp://hdl.handle.net/10722/157611
ISSN
2015 Impact Factor: 11.711
2015 SCImago Journal Rankings: 4.752
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorBanaudha, Ken_US
dc.contributor.authorKaliszewski, Men_US
dc.contributor.authorKorolnek, Ten_US
dc.contributor.authorFlorea, Len_US
dc.contributor.authorYeung, MLen_US
dc.contributor.authorJeang, KTen_US
dc.contributor.authorKumar, Aen_US
dc.date.accessioned2012-08-08T08:51:40Z-
dc.date.available2012-08-08T08:51:40Z-
dc.date.issued2011en_US
dc.identifier.citationHepatology, 2011, v. 53 n. 1, p. 53-61en_US
dc.identifier.issn0270-9139en_US
dc.identifier.urihttp://hdl.handle.net/10722/157611-
dc.description.abstractMicroRNAs (miRNAs) are approximately 22-nucleotide noncoding RNAs that constitute silencers of target gene expression. Aberrant expression of miRNA has been linked to a variety of cancers, including hepatocellular carcinoma (HCC). Hepatitis C virus (HCV) infection is considered a major cause of chronic liver disease and HCC, although the mechanism of virus infection-associated hepatocarcinogenesis remains unclear. We report a direct role of miRNAs induced in HCV-infected primary human hepatocytes that target the tumor suppressor gene DLC-1 (a Rho GTPase-activating protein), which is frequently deleted in HCC, and other solid human tumors. MicroRNA miR-141 that targets DLC-1 was accentuated in cells infected with HCV genotypes 1a, 1b, and 2a. We present several lines of evidence that efficient HCV replication requires miR-141-mediated suppression of DLC-1. An increase in miR-141 correlated with the inhibition of DLC-1 protein in HCV-infected cells. Depletion of miR-141 with oligonucleotides complementary to the miRNAs inhibited virus replication, whereas artificially increased levels of intracellular miR-141 enhanced HCV replication. HCV-infected hepatocytes showed enhanced cell proliferation that can be countered by overexpression of DLC-1. Conclusion: The collective results of this study suggest a novel mechanism of HCV infection-associated miRNA-mediated regulation of a tumor suppressor protein that has the ability to influence cell proliferation and HCV infection-mediated liver cancer. © 2010 American Association for the Study of Liver Diseases.en_US
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/en_US
dc.relation.ispartofHepatologyen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshCoculture Techniquesen_US
dc.subject.meshGtpase-Activating Proteins - Geneticsen_US
dc.subject.meshHepacivirus - Physiologyen_US
dc.subject.meshHepatocytes - Virologyen_US
dc.subject.meshHumansen_US
dc.subject.meshMicrornas - Pharmacology - Physiologyen_US
dc.subject.meshRna Interference - Physiologyen_US
dc.subject.meshTumor Suppressor Proteins - Geneticsen_US
dc.subject.meshVirus Replication - Drug Effects - Geneticsen_US
dc.titleMicroRNA silencing of tumor suppressor DLC-1 promotes efficient hepatitis C virus replication in primary human hepatocytesen_US
dc.typeArticleen_US
dc.identifier.emailYeung, ML:pmlyeung@hku.hken_US
dc.identifier.authorityYeung, ML=rp01402en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1002/hep.24016en_US
dc.identifier.pmid20967756-
dc.identifier.scopuseid_2-s2.0-78751560528en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78751560528&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume53en_US
dc.identifier.issue1en_US
dc.identifier.spage53en_US
dc.identifier.epage61en_US
dc.identifier.isiWOS:000286406300008-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridBanaudha, K=36973431400en_US
dc.identifier.scopusauthoridKaliszewski, M=6602285424en_US
dc.identifier.scopusauthoridKorolnek, T=36080587600en_US
dc.identifier.scopusauthoridFlorea, L=6603863491en_US
dc.identifier.scopusauthoridYeung, ML=8350940900en_US
dc.identifier.scopusauthoridJeang, KT=7004824803en_US
dc.identifier.scopusauthoridKumar, A=36080712400en_US
dc.identifier.citeulike8380498-

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