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dc.contributor.authorCifdaloz, Metehan
dc.contributor.authorOsterloh, Lisa
dc.contributor.authorGraña Castro, Osvaldo 
dc.contributor.authorRiveiro-Falkenbach, Erica
dc.contributor.authorXimenez-Embun, Pilar 
dc.contributor.authorMuoz Peralta, Javier 
dc.contributor.authorTejedo, Cristina
dc.contributor.authorCalvo, Tonantzin G
dc.contributor.authorKarras, Panagiotis
dc.contributor.authorOlmeda, David 
dc.contributor.authorMiñana, Belén
dc.contributor.authorGómez-López, Gonzalo 
dc.contributor.authorCañón, Estela
dc.contributor.authorEyras, Eduardo
dc.contributor.authorGuo, Haihong
dc.contributor.authorKappes, Ferdinand
dc.contributor.authorOrtiz-Romero, Pablo L
dc.contributor.authorRodríguez-Peralto, Jose L
dc.contributor.authorMegias Vazquez, Diego 
dc.contributor.authorValcárcel, Juan
dc.contributor.authorSoengas, MS 
dc.date.accessioned2019-01-28T12:54:54Z
dc.date.available2019-01-28T12:54:54Z
dc.date.issued2017
dc.identifier.citationNat Commun. 2017; 8(1):2249.es_ES
dc.identifier.issn2041-1723es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/7015
dc.description.abstractMelanomas are well-known for their altered mRNA expression profiles. Yet, the specific contribution of mRNA binding proteins (mRBPs) to melanoma development remains unclear. Here we identify a cluster of melanoma-enriched genes under the control of CUGBP Elav-like family member 1 (CELF1). CELF1 was discovered with a distinct prognostic value in melanoma after mining the genomic landscape of the 692 known mRBPs across different cancer types. Genome-wide transcriptomic, proteomic, and RNA-immunoprecipitation studies, together with loss-of-function analyses in cell lines, and histopathological evaluation in clinical biopsies, revealed an intricate repertoire of CELF1-RNA interactors with minimal overlap with other malignancies. This systems approach uncovered the oncogene DEK as an unexpected target and downstream effector of CELF1. Importantly, CELF1 and DEK were found to represent early-induced melanoma genes and adverse indicators of overall patient survival. These results underscore novel roles of CELF1 in melanoma, illustrating tumor type-restricted functions of RBPs in cancer.es_ES
dc.description.sponsorshipThe authors thank the colleagues in the CNIO Melanoma Group, in particular Eva Pérez- Guijarro, Raúl Martinez, Ángel Colmenar, Direna Alonso-Curbelo and David Sáenz for their help and support; Manuel Pérez from CNIO Confocal Microscopy Unit for immunofluorescent image capture, and the i+12 Biobank of the Hospital 12 de Octubre for providing melanoma patient samples. We also thank Endre Sebestyen for help with genomic analyses of mRBPs in cancer cells; as well as José A Esteban (CBMSO, Madrid), for critical reading of this manuscript. M.S.S. was funded by Marató TVE, Consolider RNAREG (CSD2009-00080), and SAF2014-56868-R (Spanish Ministry of Economy and Innovation). J.V. was funded by Fundación Botín, Banco de Santander through its Santander Universities Global Division, Consolider RNAREG (CSD2009-00080), AGAUR and the European Research Council, and acknowledges support of the Spanish Ministry of Economy and Competitiveness, Centro de Excelencia Severo Ochoa 2013- 2017. J.L.R.-P. was funded by grant FIS 2014/1737, and P.L.O.-R. by FIS 14/1784 from the Spanish Ministry of Health. E.E. was funded by grants BIO2011-23920, Consolider RNAREG (CSD2009-00080), by AGAUR (2014-SGR1121) and by the Sandra Ibarra Foundation for Cancer (FSI2013). The CNIO Proteomics Unit belongs to ProteoRed, PRB2- ISCIII, supported by grant PT13/0001. J.M. was supported by the Ramon y Cajal Programme (MINECO) RYC-2012-10651. H.G. and F.K. were funded by the China Scholarship Council, the Deutsche Forschungsgemeinschaft (DFG KA 2799/1) and the START Program of the Faculty of Medicine of the RWTH Aachen University. M.C. and P.K. were funded by predoctoral fellowships from Fundación La Caixa, and C.T. from SAF2014-56868-R. E.R.-F. was a recipient of a postdoctoral fellowship from “FundaciónCientífica de la Asociación Española Contra el Cáncer”and was also supported by FMM-2013/0075 of Fundacion Mutua Madrileña.es_ES
dc.language.isoenges_ES
dc.publisherNature Publishing Group es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.mesh3' Untranslated Regions es_ES
dc.subject.meshBiopsy es_ES
dc.subject.meshCELF1 Protein es_ES
dc.subject.meshCell Line, Tumor es_ES
dc.subject.meshCell Proliferation es_ES
dc.subject.meshChromosomal Proteins, Non-Histone es_ES
dc.subject.meshHumans es_ES
dc.subject.meshImmunoprecipitation es_ES
dc.subject.meshMelanoma es_ES
dc.subject.meshOncogene Proteins es_ES
dc.subject.meshPoly-ADP-Ribose Binding Proteins es_ES
dc.subject.meshPrognosis es_ES
dc.subject.meshProteomics es_ES
dc.subject.meshRNA, Neoplasm es_ES
dc.subject.meshSurvival Analysis es_ES
dc.subject.meshTranscriptome es_ES
dc.subject.meshOncogenes es_ES
dc.subject.meshSystems Biology es_ES
dc.titleSystems analysis identifies melanoma-enriched pro-oncogenic networks controlled by the RNA binding protein CELF1es_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID29269732es_ES
dc.format.volume8es_ES
dc.format.number1es_ES
dc.format.page2249es_ES
dc.identifier.doi10.1038/s41467-017-02353-yes_ES
dc.contributor.funderMinisterio de Ciencia e Innovación (España) 
dc.contributor.funderBotín Foundation 
dc.contributor.funderUnión Europea. Comisión Europea. European Research Council (ERC) 
dc.contributor.funderMinisterio de Sanidad y Consumo (España) 
dc.contributor.funderFundación La Caixa 
dc.contributor.funderFundación La Marató TV3 
dc.contributor.funderAsociación Española Contra el Cáncer 
dc.contributor.funderFundación Mutua Madrileña 
dc.description.peerreviewedes_ES
dc.identifier.e-issn2041-1723es_ES
dc.relation.publisherversionhttps://doi.org/10.1038/s41467-017-02353-y.es_ES
dc.identifier.journalNature communicationses_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Melanomaes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2014-56868-Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/FIS 2014/1737es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/FIS 14/1784es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PT13/0001es_ES
dc.rights.accessRightsopen accesses_ES


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