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dc.contributor.authorSmith, Stephenen
dc.contributor.authorScarpini, Cinziaen
dc.contributor.authorGroves, Ianen
dc.contributor.authorOdle, Richard Ien
dc.contributor.authorColeman, Nicholasen
dc.date.accessioned2016-08-01T12:58:11Z
dc.date.available2016-08-01T12:58:11Z
dc.date.issued2016-07-26en
dc.identifier.issn2045-2322
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/256925
dc.description.abstractDevelopment of cervical squamous cell carcinoma requires increased expression of the major high-risk human-papillomavirus (HPV) oncogenes E6 and E7 in basal cervical epithelial cells. We used a systems biology approach to identify host transcriptional networks in such cells and study the concentration-dependent changes produced by HPV16-E6 and -E7 oncoproteins. We investigated sample sets derived from the W12 model of cervical neoplastic progression, for which high quality phenotype/genotype data were available. We defined a gene co-expression matrix containing a small number of highly-connected hub nodes that controlled large numbers of downstream genes (regulons), indicating the scale-free nature of host gene co-expression in W12. We identified a small number of ‘master regulators’ for which downstream effector genes were significantly associated with protein levels of HPV16 E6 (n=7) or HPV16 E7 (n=5). We validated our data by depleting E6/E7 in relevant cells and by functional analysis of selected genes $\textit{in vitro}$. We conclude that the network of transcriptional interactions in HPV16-infected basal-type cervical epithelium is regulated in a concentration-dependent manner by E6/E7, via a limited number of central master-regulators. These effects are likely to be significant in cervical carcinogenesis, where there is competitive selection of cells with elevated expression of virus oncoproteins.
dc.description.sponsorshipCancer Research UK (Programme Grant A13080)
dc.languageEnglishen
dc.language.isoenen
dc.publisherNature Publishing Group
dc.rightsAttribution 4.0 International*
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectcervical canceren
dc.subjectoncogenesen
dc.subjecttumour virus infectionsen
dc.titleIdentification of host transcriptional networks showing concentration-dependent regulation by HPV16 E6 and E7 proteins in basal cervical squamous epithelial cellsen
dc.typeArticle
dc.description.versionThis is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/srep29832en
prism.number29832en
prism.publicationDate2016en
prism.publicationNameScientific Reportsen
prism.volume6en
dc.identifier.doi10.17863/CAM.858
dcterms.dateAccepted2016-06-22en
rioxxterms.versionofrecord10.1038/srep29832en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2016-07-26en
dc.contributor.orcidSmith, Stephen [0000-0001-7744-3238]
dc.contributor.orcidScarpini, Cinzia [0000-0003-4730-5197]
dc.contributor.orcidGroves, Ian [0000-0001-8882-6701]
dc.identifier.eissn2045-2322
rioxxterms.typeJournal Article/Reviewen
cam.orpheus.successThu Jan 30 12:57:30 GMT 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2100-01-01


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International