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dc.contributor.authorDíaz-Martínez, Martaes_ES
dc.contributor.authorBenito-Jardón, Lucíaes_ES
dc.contributor.authorAlonso, Lolaes_ES
dc.contributor.authorKoetz-Ploch, Lisaes_ES
dc.contributor.authorHernando, Evaes_ES
dc.contributor.authorTeixidó, Joaquínes_ES
dc.date.accessioned2018-03-07T13:36:11Z-
dc.date.available2018-03-07T13:36:11Z-
dc.date.issued2018-02-15-
dc.identifier.citationCancer Res 78(4):1017-1030 (2018)es_ES
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10261/161797-
dc.description42 p.-7 fig.es_ES
dc.description.abstractMelanoma treatment with the BRAF V600E inhibitor vemurafenib provides therapeutic benefits but the common emergence of drug resistance remains a challenge. We generated A375 melanoma cells resistant to vemurafenib with the goal of investigating changes in miRNA expression patterns that might contribute to resistance. Increased expression of miR-204-5p and miR-211-5p occurring in vemurafenib-resistant cells was determined to impact vemurafenib response. Their expression was rapidly affected by vemurafenib treatment through RNA stabilization. Similar effects were elicited by MEK and ERK inhibitors but not AKT or Rac inhibitors. Ectopic expression of both miRNA in drug-naïve human melanoma cells was sufficient to confer vemurafenib resistance and more robust tumor growth in vivo Conversely, silencing their expression in resistant cells inhibited cell growth. Joint overexpression of miR-204-5p and miR-211-5p durably stimulated Ras and MAPK upregulation after vemurafenib exposure. Overall, our findings show how upregulation of miR-204-5p and miR-211-5p following vemurafenib treatment enables the emergence of resistance, with potential implications for mechanism-based strategies to improve vemurafenib responses.Significance: Identification of miRNAs that enable resistance to BRAF inhibitors in melanoma suggests a mechanism-based strategy to limit resistance and improve clinical outcomes.es_ES
dc.description.sponsorshipThis work was supported by grants SAF2014-53059-R and RD12/0036/0061 to J. Teixidó, and NIH/NCI grants R01CA155234-03 and R01CA163891-03 to E. Hernando.es_ES
dc.language.isoenges_ES
dc.publisherAmerican Association for Cancer Researches_ES
dc.relationMINECO/ICTI2013-2016/SAF2014-53059-Res_ES
dc.relation.isversionofPostprintes_ES
dc.rightsopenAccessen_EN
dc.subjectMelanomaes_ES
dc.subjectmiRNAes_ES
dc.subjectBRAF inhibitores_ES
dc.subjectResistancees_ES
dc.subjectMAP kinaseses_ES
dc.titlemiR-204-5p and miR-211-5p contribute to BRAF inhibitor resistance in melanomaes_ES
dc.title.alternativemiRNA contribution to BRAF inhibitor melanoma resistancees_ES
dc.typeartículoes_ES
dc.identifier.doi10.1158/0008-5472.CAN-17-1318-
dc.description.peerreviewedPeer reviewedes_ES
dc.relation.publisherversionhttp://dx.doi.org/10.1158/0008-5472.CAN-17-1318es_ES
dc.identifier.e-issn1538-7445-
dc.embargo.terms2019-02-15es_ES
dc.contributor.funderMinisterio de Economía y Competitividad (España)es_ES
dc.contributor.funderNational Cancer Institute (US)es_ES
dc.contributor.funderNational Institutes of Health (US)es_ES
dc.relation.csices_ES
oprm.item.hasRevisionno ko 0 false*
dc.identifier.funderhttp://dx.doi.org/10.13039/100000002es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100003329es_ES
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