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dc.contributor.authorCorreia, Nádia C
dc.contributor.authorMelão, Alice
dc.contributor.authorPóvoa, Vanda
dc.contributor.authorSarmento, Leonor
dc.contributor.authorGómez de Cedrón, Marta
dc.contributor.authorMalumbres, Marcos
dc.contributor.authorEnguita, Francisco J
dc.contributor.authorBarata, João T
dc.date.accessioned2020-07-16T15:14:42Z
dc.date.available2020-07-16T15:14:42Z
dc.date.issued2016-02-16
dc.identifier.citationOncotarget . 2016 ;7(7):8268-81es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/10796
dc.description.abstractThe transcription factor TAL1 is a proto-oncogene whose aberrant expression in committed T-cell precursors is associated with the development of T-cell acute lymphoblastic leukemia (T-ALL). The mechanisms leading to aberrant activation of TAL1 in T-ALL patients who lack chromosomal rearrangements involving the TAL1 locus remain largely unknown. We hypothesized that TAL1 levels decrease during normal T-cell development at least in part due to miRNA-dependent silencing, in which case TAL1 over-expression in some T-ALL cases could be the consequence of deregulated miRNA expression. By performing computational prediction of miRNAs that bind to the human TAL1 mRNA we compiled a list of miRNAs that are candidates to regulate TAL1. Using a luciferase reporter system and mutagenesis assays we confirmed the miRNA-TAL1 mRNA interactions and selected candidate miRNAs: miR-101, miR-520d-5p, miR-140-5p, miR-448 and miR-485-5p. Over-expression of these microRNAs in different T-ALL cell lines consistently resulted in the down-regulation of TAL1 protein. In accordance, inhibition of miR-101 and miR-520d-5p promoted TAL1 protein expression. Importantly, we found that miR-101, miR-140-5p, miR-448 and miR-485-5p were down-regulated in T-ALL patient specimens and T-ALL cell lines. Our results show for the first time the existence of epigenetic regulation of TAL1 by specific miRNAs which may contribute, at least in part, to the ectopic expression of TAL1 in some T-ALL cases.es_ES
dc.description.sponsorshipThese studies were financed by Liga Portuguesa Contra o Cancro (Terry Fox Award) and by Fundacao para a Ciencia e a Tecnologia (project PTDC/BIM-ONC/1548/2012). NCC received an FCT-SFRH PhD fellowship. JTB is supported by an FCT Consolidation Grant. The Cell Division and Cancer group of the CNIO is funded by the Spanish Ministry of Economy and Competitiveness (MINECO; SAF2012-38215: Consolider-Ingenio 2010 Programme SAF2014-57791-REDC; Red Tematica CellSYS BFU2014-52125-REDT), and the Comunidad de Madrid (OncoCycle Programme S2010/BMD-2470).
dc.language.isoenges_ES
dc.publisherIMPACT JOURNALS LLCes_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshGene Expression Regulation, Leukemic es_ES
dc.subject.mesh3' Untranslated Regions es_ES
dc.subject.meshBasic Helix-Loop-Helix Transcription Factors es_ES
dc.subject.meshBlotting, Westernes_ES
dc.subject.meshCell Differentiation es_ES
dc.subject.meshEpigenesis, Genetices_ES
dc.subject.meshGene Expression Profiling es_ES
dc.subject.meshHumans es_ES
dc.subject.meshMicroRNAs es_ES
dc.subject.meshPrecursor T-Cell Lymphoblastic Leukemia-Lymphoma es_ES
dc.subject.meshProto-Oncogene Proteins es_ES
dc.subject.meshRNA, Messenger es_ES
dc.subject.meshReal-Time Polymerase Chain Reaction es_ES
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction es_ES
dc.subject.meshT-Cell Acute Lymphocytic Leukemia Protein 1 es_ES
dc.subject.meshTumor Cells, Culturedes_ES
dc.titlemicroRNAs regulate TAL1 expression in T-cell acute lymphoblastic leukemia.es_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID26882564es_ES
dc.format.volume7es_ES
dc.format.number7es_ES
dc.format.page8268-81es_ES
dc.identifier.doi10.18632/oncotarget.6987es_ES
dc.contributor.funderPortuguese Foundation for Science and Technologyes_ES
dc.contributor.funderMinisterio de Economia y Competitividad (MINECO)es_ES
dc.contributor.funderConsolider-Ingenio Programmees_ES
dc.contributor.funderComunidad de Madrides_ES
dc.contributor.funderRed Tematica CellSYSes_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn1949-2553es_ES
dc.relation.publisherversionhttps://doi.org/10.18632/oncotarget.6987.es_ES
dc.identifier.journalOncotargetes_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de División Celular y Cánceres_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/SAF2012-38215es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/SAF2014-57791-REDCes_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/BFU2014-52125-REDTes_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/S2010/BMD-2470es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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Atribución-NoComercial-CompartirIgual 4.0 Internacional
This item is licensed under a: Atribución-NoComercial-CompartirIgual 4.0 Internacional