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dc.contributor.authorO'Driscoll, Lorraineen
dc.date.accessioned2015-11-20T15:41:21Z
dc.date.available2015-11-20T15:41:21Z
dc.date.issued2015en
dc.date.submitted2015en
dc.identifier.citationO'Brien K, Lowry MC, Corcoran C, Martinez VG, Daly M, Rani S, Gallagher WM, Radomski MW, MacLeod RA, O'Driscoll L., miR-134 in extracellular vesicles reduces triple-negative breast cancer aggression and increases drug sensitivity., Oncotarget, 6, 32, 2015, 32774 - 32789en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/74877
dc.descriptionPUBLISHEDen
dc.description.abstractExosomes (EVs) have relevance in cell-to-cell communication carrying pro- tumorigenic factors that participate in oncogenesis and drug resistance and are proposed to have potential as self-delivery systems. Advancing on our studies of EVs in triple-negative breast cancer, here we more comprehensively analysed isogenic cell line variants and their EV populations, tissues cell line variants and their EV populations, as well as breast tumour and normal tissues. Profiling 384 miRNAs showed EV miRNA content to be highly representative of their cells of origin. miRNAs most substantially down-regulated in aggressive cells and their EVs originated from 14q32. Analysis of miR-134, the most substantially down-regulated miRNA, supported its clinical relevance in breast tumours compared to matched normal breast tissue. Functional studies indicated that miR-134 controls STAT5B which, in turn, controls Hsp90. miR-134 delivered by direct transfection into Hs578Ts(i) 8 cells (in which it was greatly down-regulated) reduced STAT5B, Hsp90, and Bcl-2 levels, reduced cellular proliferation, and enhanced cisplatin-induced apoptosis. Delivery via miR-134-enriched EVs also reduced STAT5B and Hsp90, reduced cellular migration and invasion, and enhanced sensitivity to anti-Hsp90 drugs. While the differing effects achieved by transfection or EV delivery are likely to be, at least partly, due to specific amounts of miR-134 delivered by these routes, these EV-based studies identified miRNA-134 as a potential biomarker and therapeutic for breast cancer.en
dc.format.extent32774en
dc.format.extent32789en
dc.language.isoenen
dc.relation.ispartofseriesOncotargeten
dc.relation.ispartofseries6en
dc.relation.ispartofseries32en
dc.rightsYen
dc.titlemiR-134 in extracellular vesicles reduces triple-negative breast cancer aggression and increases drug sensitivity.en
dc.typeJournal Articleen
dc.contributor.sponsorHealth Research Board (HRB)en
dc.contributor.sponsorIrish Cancer Societyen
dc.contributor.sponsorEuropean Union (EU)en
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/lodriscen
dc.identifier.rssinternalid107697en
dc.identifier.doi10.18632/oncotarget.5192.en
dc.relation.ecprojectidinfo:eu-repo/grantAgreement/EC/FP7/CCRC13GAL
dc.rights.ecaccessrightsopenAccess
dc.contributor.sponsorGrantNumberHRA_POR/2013/342en
dc.contributor.sponsorGrantNumberCCRC13GALen
dc.subject.TCDThemeCanceren
dc.subject.TCDThemeGenes & Societyen
dc.subject.TCDTagANTICANCER DRUGSen
dc.subject.TCDTagBREAST CANCERen
dc.subject.TCDTagexosomesen
dc.identifier.rssurihttp://www.ncbi.nlm.nih.gov/pubmed/26416415en
dc.identifier.orcid_id0000-0002-9860-8262en


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