dc.contributor.author | Carotenuto, P | |
dc.contributor.author | Amato, F | |
dc.contributor.author | Lampis, A | |
dc.contributor.author | Rae, C | |
dc.contributor.author | Hedayat, S | |
dc.contributor.author | Previdi, MC | |
dc.contributor.author | Zito, D | |
dc.contributor.author | Raj, M | |
dc.contributor.author | Guzzardo, V | |
dc.contributor.author | Sclafani, F | |
dc.contributor.author | Lanese, A | |
dc.contributor.author | Parisi, C | |
dc.contributor.author | Vicentini, C | |
dc.contributor.author | Said-Huntingford, I | |
dc.contributor.author | Hahne, JC | |
dc.contributor.author | Hallsworth, A | |
dc.contributor.author | Kirkin, V | |
dc.contributor.author | Young, K | |
dc.contributor.author | Begum, R | |
dc.contributor.author | Wotherspoon, A | |
dc.contributor.author | Kouvelakis, K | |
dc.contributor.author | Azevedo, SX | |
dc.contributor.author | Michalarea, V | |
dc.contributor.author | Upstill-Goddard, R | |
dc.contributor.author | Rao, S | |
dc.contributor.author | Watkins, D | |
dc.contributor.author | Starling, N | |
dc.contributor.author | Sadanandam, A | |
dc.contributor.author | Chang, DK | |
dc.contributor.author | Biankin, AV | |
dc.contributor.author | Jamieson, NB | |
dc.contributor.author | Scarpa, A | |
dc.contributor.author | Cunningham, D | |
dc.contributor.author | Chau, I | |
dc.contributor.author | Workman, P | |
dc.contributor.author | Fassan, M | |
dc.contributor.author | Valeri, N | |
dc.contributor.author | Braconi, C | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2021-11-30T10:36:11Z | |
dc.date.available | 2021-11-30T10:36:11Z | |
dc.date.issued | 2021-11-18 | |
dc.identifier | https://www.ncbi.nlm.nih.gov/pubmed/34795259 | |
dc.identifier | 10.1038/s41467-021-27099-6 | |
dc.identifier.citation | Nat Commun, 2021, 12 (1), pp. 6738 - ? | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4903 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.doi | 10.1038/s41467-021-27099-6 | |
dc.description.abstract | FOLFIRINOX, a combination of chemotherapy drugs (Fluorouracil, Oxaliplatin, Irinotecan -FOI), provides the best clinical benefit in pancreatic ductal adenocarcinoma (PDAC) patients. In this study we explore the role of miRNAs (MIR) as modulators of chemosensitivity to identify potential biomarkers of response. We find that 41 and 84 microRNA inhibitors enhance the sensitivity of Capan1 and MiaPaCa2 PDAC cells respectively. These include a MIR1307-inhibitor that we validate in further PDAC cell lines. Chemotherapy-induced apoptosis and DNA damage accumulation are higher in MIR1307 knock-out (MIR1307KO) versus control PDAC cells, while re-expression of MIR1307 in MIR1307KO cells rescues these effects. We identify binding of MIR1307 to CLIC5 mRNA through covalent ligation of endogenous Argonaute-bound RNAs cross-linking immunoprecipitation assay. We validate these findings in an in vivo model with MIR1307 disruption. In a pilot cohort of PDAC patients undergoing FOLFIRONX chemotherapy, circulating MIR1307 correlates with clinical outcome. | |
dc.format.extent | 6738 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PORTFOLIO | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | Modulation of pancreatic cancer cell sensitivity to FOLFIRINOX through microRNA-mediated regulation of DNA damage. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2021-10-29 | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1038/s41467-021-27099-6 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2021-11-18 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Nat Commun | |
pubs.issue | 1 | |
pubs.notes | No embargo | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/ImmNet | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Signal Transduction & Molecular Pharmacology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Evolutionary Genomics & Modelling | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Gastrointestinal Cancer Biology and Genomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Systems and Precision Cancer Medicine | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.organisational-group | /ICR/Students | |
pubs.organisational-group | /ICR/Students/PhD and MPhil | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/13/14 Starting Cohort | |
pubs.publication-status | Published online | |
pubs.volume | 12 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Signal Transduction & Molecular Pharmacology | |
icr.researchteam | Medicine (RMH Smith Cunningham) | |
icr.researchteam | Evolutionary Genomics & Modelling | |
icr.researchteam | Gastrointestinal Cancer Biology and Genomics | |
icr.researchteam | Systems and Precision Cancer Medicine | |
dc.contributor.icrauthor | Lampis, Andrea | |
dc.contributor.icrauthor | Hahne, Jens | |
dc.contributor.icrauthor | Workman, Paul | |
dc.contributor.icrauthor | Valeri, Nicola | |