Show simple item record

dc.contributor.authorHattori, Hiroyoshi
dc.contributor.authorJanky, Rekin's
dc.contributor.authorNietfeld, Wilfried
dc.contributor.authorAerts, Stein
dc.contributor.authorMadan Babu, M
dc.contributor.authorVenkitaraman, Ashok
dc.date.accessioned2020-02-14T00:30:19Z
dc.date.available2020-02-14T00:30:19Z
dc.date.issued2014
dc.identifier.issn1538-4101
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/302109
dc.description.abstractThe human DNA damage response (DDR) triggers profound changes in gene expression, whose nature and regulation remain uncertain. Although certain micro-(mi)RNA species including miR34, miR-18, miR-16 and miR-143 have been implicated in the DDR, there is as yet no comprehensive description of genome-wide changes in the expression of miRNAs triggered by DNA breakage in human cells. We have used next-generation sequencing (NGS), combined with rigorous integrative computational analyses, to describe genome-wide changes in the expression of miRNAs during the human DDR. The changes affect 150 of 1523 miRNAs known in miRBase v18 from 4-24 h after the induction of DNA breakage, in cell-type dependent patterns. The regulatory regions of the most-highly regulated miRNA species are enriched in conserved binding sites for p53. Indeed, genome-wide changes in miRNA expression during the DDR are markedly altered in TP53-/- cells compared to otherwise isogenic controls. The expression levels of certain damage-induced, p53-regulated miRNAs in cancer samples correlate with patient survival. Our work reveals genome-wide and cell type-specific alterations in miRNA expression during the human DDR, which are regulated by the tumor suppressor protein p53. These findings provide a genomic resource to identify new molecules and mechanisms involved in the DDR, and to examine their role in tumor suppression and the clinical outcome of cancer patients.
dc.format.mediumPrint
dc.languageeng
dc.publisherInforma UK Limited
dc.rightsAttribution-NonCommercial 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/
dc.subjectCell Line
dc.subjectHumans
dc.subjectNeoplasms
dc.subjectDNA Damage
dc.subjectMicroRNAs
dc.subjectOrgan Specificity
dc.subjectDNA Repair
dc.subjectGene Expression Regulation
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectGenome
dc.subjectGenome, Human
dc.subjectTumor Suppressor Protein p53
dc.titlep53 shapes genome-wide and cell type-specific changes in microRNA expression during the human DNA damage response.
dc.typeArticle
prism.endingPage2586
prism.issueIdentifier16
prism.publicationDate2014
prism.publicationNameCell Cycle
prism.startingPage2572
prism.volume13
dc.identifier.doi10.17863/CAM.49185
rioxxterms.versionofrecord10.4161/15384101.2015.942209
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2014-01
dc.contributor.orcidAerts, Stein [0000-0002-8006-0315]
dc.identifier.eissn1551-4005
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (G1001521)
pubs.funder-project-idMedical Research Council (G1001522)
pubs.funder-project-idMedical Research Council (MC_UU_12022/1)
pubs.funder-project-idMRC (MC_UU_12022/8)
cam.issuedOnline2014-10-30


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

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