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Article: An Oncogenomics-Based In Vivo RNAi Screen Identifies Tumor Suppressors in Liver Cancer

TitleAn Oncogenomics-Based In Vivo RNAi Screen Identifies Tumor Suppressors in Liver Cancer
Authors
Issue Date2008
PublisherCell Press. The Journal's web site is located at http://www.elsevier.com/locate/cell
Citation
Cell, 2008, v. 135 n. 5, p. 852-864 How to Cite?
AbstractCancers are highly heterogeneous and contain many passenger and driver mutations. To functionally identify tumor suppressor genes relevant to human cancer, we compiled pools of short hairpin RNAs (shRNAs) targeting the mouse orthologs of genes recurrently deleted in a series of human hepatocellular carcinomas and tested their ability to promote tumorigenesis in a mosaic mouse model. In contrast to randomly selected shRNA pools, many deletion-specific pools accelerated hepatocarcinogenesis in mice. Through further analysis, we identified and validated 13 tumor suppressor genes, 12 of which had not been linked to cancer before. One gene, XPO4, encodes a nuclear export protein whose substrate, EIF5A2, is amplified in human tumors, is required for proliferation of XPO4-deficient tumor cells, and promotes hepatocellular carcinoma in mice. Our results establish the feasibility of in vivo RNAi screens and illustrate how combining cancer genomics, RNA interference, and mosaic mouse models can facilitate the functional annotation of the cancer genome. © 2008 Elsevier Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/172981
ISSN
2015 Impact Factor: 28.71
2015 SCImago Journal Rankings: 28.188
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorZender, Len_US
dc.contributor.authorXue, Wen_US
dc.contributor.authorZuber, Jen_US
dc.contributor.authorSemighini, CPen_US
dc.contributor.authorKrasnitz, Aen_US
dc.contributor.authorMa, Ben_US
dc.contributor.authorZender, Pen_US
dc.contributor.authorKubicka, Sen_US
dc.contributor.authorLuk, JMen_US
dc.contributor.authorSchirmacher, Pen_US
dc.contributor.authorRichard Mccombie, Wen_US
dc.contributor.authorWigler, Men_US
dc.contributor.authorHicks, Jen_US
dc.contributor.authorHannon, GJen_US
dc.contributor.authorPowers, Sen_US
dc.contributor.authorLowe, SWen_US
dc.date.accessioned2012-10-30T06:26:11Z-
dc.date.available2012-10-30T06:26:11Z-
dc.date.issued2008en_US
dc.identifier.citationCell, 2008, v. 135 n. 5, p. 852-864en_US
dc.identifier.issn0092-8674en_US
dc.identifier.urihttp://hdl.handle.net/10722/172981-
dc.description.abstractCancers are highly heterogeneous and contain many passenger and driver mutations. To functionally identify tumor suppressor genes relevant to human cancer, we compiled pools of short hairpin RNAs (shRNAs) targeting the mouse orthologs of genes recurrently deleted in a series of human hepatocellular carcinomas and tested their ability to promote tumorigenesis in a mosaic mouse model. In contrast to randomly selected shRNA pools, many deletion-specific pools accelerated hepatocarcinogenesis in mice. Through further analysis, we identified and validated 13 tumor suppressor genes, 12 of which had not been linked to cancer before. One gene, XPO4, encodes a nuclear export protein whose substrate, EIF5A2, is amplified in human tumors, is required for proliferation of XPO4-deficient tumor cells, and promotes hepatocellular carcinoma in mice. Our results establish the feasibility of in vivo RNAi screens and illustrate how combining cancer genomics, RNA interference, and mosaic mouse models can facilitate the functional annotation of the cancer genome. © 2008 Elsevier Inc. All rights reserved.en_US
dc.languageengen_US
dc.publisherCell Press. The Journal's web site is located at http://www.elsevier.com/locate/cellen_US
dc.relation.ispartofCellen_US
dc.subject.meshAnimalsen_US
dc.subject.meshCarcinoma, Hepatocellular - Geneticsen_US
dc.subject.meshGenes, Tumor Suppressoren_US
dc.subject.meshGenomicsen_US
dc.subject.meshHumansen_US
dc.subject.meshKaryopherins - Genetics - Metabolismen_US
dc.subject.meshLiver Neoplasms - Geneticsen_US
dc.subject.meshMiceen_US
dc.subject.meshPeptide Initiation Factors - Geneticsen_US
dc.subject.meshRna Interferenceen_US
dc.subject.meshRna, Untranslated - Geneticsen_US
dc.subject.meshRna-Binding Proteins - Geneticsen_US
dc.subject.meshSmad3 Protein - Metabolismen_US
dc.titleAn Oncogenomics-Based In Vivo RNAi Screen Identifies Tumor Suppressors in Liver Canceren_US
dc.typeArticleen_US
dc.identifier.emailLuk, JM: jmluk@hkucc.hku.hken_US
dc.identifier.authorityLuk, JM=rp00349en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.cell.2008.09.061en_US
dc.identifier.pmid19012953-
dc.identifier.scopuseid_2-s2.0-56349121125en_US
dc.identifier.hkuros152264-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-56349121125&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume135en_US
dc.identifier.issue5en_US
dc.identifier.spage852en_US
dc.identifier.epage864en_US
dc.identifier.isiWOS:000261183900017-
dc.publisher.placeUnited Statesen_US
dc.identifier.f10001138090-
dc.identifier.scopusauthoridZender, L=6603035987en_US
dc.identifier.scopusauthoridXue, W=32267773000en_US
dc.identifier.scopusauthoridZuber, J=7005247940en_US
dc.identifier.scopusauthoridSemighini, CP=6507074032en_US
dc.identifier.scopusauthoridKrasnitz, A=7003460476en_US
dc.identifier.scopusauthoridMa, B=7403300702en_US
dc.identifier.scopusauthoridZender, P=25639138900en_US
dc.identifier.scopusauthoridKubicka, S=7004286738en_US
dc.identifier.scopusauthoridLuk, JM=7006777791en_US
dc.identifier.scopusauthoridSchirmacher, P=7005272237en_US
dc.identifier.scopusauthoridRichard McCombie, W=8309940100en_US
dc.identifier.scopusauthoridWigler, M=7005241418en_US
dc.identifier.scopusauthoridHicks, J=35324456000en_US
dc.identifier.scopusauthoridHannon, GJ=7006115520en_US
dc.identifier.scopusauthoridPowers, S=7203083045en_US
dc.identifier.scopusauthoridLowe, SW=15064198100en_US
dc.identifier.citeulike3795945-

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