dc.contributor.author | SENGE, MATHIAS | en |
dc.contributor.author | REYNOLDS, JOHN | en |
dc.date.accessioned | 2017-01-18T14:59:30Z | |
dc.date.available | 2017-01-18T14:59:30Z | |
dc.date.issued | 2016 | en |
dc.date.submitted | 2016 | en |
dc.identifier.citation | Duggan S.P, Behan F.M, Kirca M, Zaheer A, McGarrigle S.A, Reynolds J.V, Vaz G.M.F, Senge M.O, Kelleher D, The characterization of an intestine-like genomic signature maintained during Barrett's-associated adenocarcinogenesis reveals an NR5A2-mediated promotion of cancer cell survival, Scientific Reports, 6, 2016, 32638 - | en |
dc.identifier.other | Y | en |
dc.identifier.uri | http://hdl.handle.net/2262/78922 | |
dc.description | PUBLISHED | en |
dc.description | Export Date: 8 December 2016 | en |
dc.description.abstract | Barrett’s oesophagus (BO), an intestinal-type metaplasia (IM), typically arising in conjunction with
gastro-oesophageal reflux disease, is a prominent risk factor for the development of oesophageal
adenocarcinoma (OAC). The molecular similarities between IM and normal intestinal tissues are
ill-defined. Consequently, the contribution of intestine-enriched factors expressed within BO to
oncogenesis is unclear. Herein, using transcriptomics we define the intestine-enriched genes expressed
in meta-profiles of BO and OAC. Interestingly, 77% of the genes differentially expressed in a metaprofile
of BO were similarly expressed in intestinal tissues. Furthermore, 85% of this intestine-like
signature was maintained upon transition to OAC. Gene networking analysis of transcription factors
within this signature revealed a network centred upon NR5A2, GATA6 and FOXA2, whose overexpression
was determined in a cohort of BO and OAC patients. Simulated acid reflux was observed
to induce the expression of both NR5A2 and GATA6. Using siRNA-mediated silencing and an
NR5A2 antagonist we demonstrate that NR5A2-mediated cancer cell survival is facilitated through
augmentation of GATA6 and anti-apoptotic factor BCL-XL levels. Abrogation of NR5A2-GATA6
expression in conjunction with BCL-XL co-silencing resulted in synergistically increased sensitivity to
chemotherapeutics and photo-dynamic therapeutics. These findings characterize the intestine-like
signature associated with IM which may have important consequences to adenocarcinogenesis. | en |
dc.description.sponsorship | HRB | en |
dc.format.extent | 32638 | en |
dc.relation.ispartofseries | Scientific Reports | en |
dc.relation.ispartofseries | 6 | en |
dc.rights | Y | en |
dc.subject | Barrett’s oesophagus | en |
dc.subject.lcsh | Barrett’s oesophagus | en |
dc.title | The characterization of an intestine-like genomic signature maintained during Barrett's-associated adenocarcinogenesis reveals an NR5A2-mediated promotion of cancer cell survival | en |
dc.type | Journal Article | en |
dc.contributor.sponsor | Health Research Board (HRB) | en |
dc.type.supercollection | scholarly_publications | en |
dc.type.supercollection | refereed_publications | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/sengem | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/reynoljv | en |
dc.identifier.rssinternalid | 137599 | en |
dc.identifier.doi | http://dx.doi.org/10.1038/srep32638 | en |
dc.rights.ecaccessrights | openAccess | |
dc.contributor.sponsorGrantNumber | HRB-TRA.2007.11 | en |
dc.identifier.rssuri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84986269486&doi=10.1038%2fsrep32638&partnerID=40&md5=a9958391484e4bc412b24c4ae5b44f3a | en |