dc.contributor.author | Bartolome-Izquierdo, Nahikari | |
dc.contributor.author | de Yebenes, Virginia G | |
dc.contributor.author | Alvarez-Prado, Angel Francisco | |
dc.contributor.author | Mur, Sonia M. | |
dc.contributor.author | Lopez, Juan Antonio | |
dc.contributor.author | Roa, Sergio | |
dc.contributor.author | Vazquez, Jesus | |
dc.contributor.author | Ramiro, Almudena R | |
dc.date.accessioned | 2017-10-20T10:23:12Z | |
dc.date.available | 2017-10-20T10:23:12Z | |
dc.date.issued | 2017 | |
dc.identifier | ISI:000400243100014 | |
dc.identifier.citation | Blood. 2017; 129(17):2408-2419 | |
dc.identifier.issn | 0006-4971 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/5121 | |
dc.description.abstract | Non-Hodgkin lymphoma comprises a variety of neoplasms, many of which arise from germinal center (GC)-experienced B cells. microRNA-28 (miR-28) is a GC-specific miRNA whose expression is lost in numerous mature B-cell neoplasms. Here we show that miR-28 regulates the GC reaction in primary B cells by impairing class switch recombination and memory B and plasma cell differentiation. Deep quantitative proteomics combined with transcriptome analysis identified miR-28 targets involved in cell-cycle and B-cell receptor signaling. Accordingly, we found that miR-28 expression diminished proliferation in primary and lymphoma cells in vitro. Importantly, miR-28 reexpression in human Burkitt (BL) and diffuse large B-cell lymphoma (DLBCL) xenografts blocked tumor growth, both when delivered in viral vectors or as synthetic, clinically amenable, molecules. Further, the antitumoral effect of miR-28 is conserved in a primary murine in vivo model of BL. Thus, miR-28 replacement is uncovered as a novel therapeutic strategy for DLBCL and BL treatment. | |
dc.description.sponsorship | This work was supported by a Ministerio de Economia y Competitividad's research training program (Formacion de Personal Investigador [FPI]) fellowship (N.B.-I.); the Ramon y Cajal program (RYC-2009-04503) funded by the Ministerio de Educacion, Cultura y Deporte and the European Research Council Proof of Concept program (HEAL-BY-MIRNA 713728) (V.G.d.Y.); the Centro Nacional de Investigaciones Cardiovaculares (CNIC) (A.F.A.-P., S.M.M., A.R.R.); the Ministerio de Economia y Competitividad (SAF2010-21394, SAF2013-42767-R), the European Research Council Starting Grant program (BCLYM-207844), and Proof of Concept program (HEAL-BY-MIRNA 713728) (A.R.R.); the People Programme-Marie Curie Actions (FP7-PIIF-2012-328177), Spanish Ministry of Economy and Competitiveness (MINECO; SAF2013-45787-R), and Gobierno de Navarra (GN-106/2014) (S.R.); and the Ministerio de Economia y Competitividad (BIO2012-37926 and BIO2015-67580-P), Instituto de Salud Carlos III (Fondo de Investigacion Sanitaria [FIS] grants PRB2 [IPT13/0001, Proteo-Red], the Fundacion La Marato TV3, and Redes tematicas de investigacion cooperativa en salud [RETICS] [RD12/0042/00056, RIC]) (J.V.). This work has been cofunded by Fondo Europeo de Desarrollo Regional (FEDER) funds. The CNIC is supported by the and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505). | |
dc.language.iso | eng | |
dc.publisher | American Society of Hematology (ASH) | |
dc.type.hasVersion | VoR | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | B-CELL LYMPHOMA | |
dc.subject | NF-KAPPA-B | |
dc.subject | INDUCED CYTIDINE DEAMINASE | |
dc.subject | GENOMIC INSTABILITY | |
dc.subject | BURKITT-LYMPHOMA | |
dc.subject | CANCER-THERAPY | |
dc.subject | C-MYC | |
dc.subject | MICRORNAS | |
dc.subject | PATHOGENESIS | |
dc.subject | EXPRESSION | |
dc.title | miR-28 regulates the germinal center reaction and blocks tumor growth in preclinical models of non-Hodgkin lymphoma | |
dc.type | journal article | |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 28188132 | |
dc.format.volume | 129 | |
dc.format.page | 2408-2419 | |
dc.identifier.doi | 10.1182/blood-2016-08-731166 | |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | |
dc.contributor.funder | Ministerio de Educación, Cultura y Deporte (España) | |
dc.contributor.funder | Unión Europea. Comisión Europea | |
dc.contributor.funder | Unión Europea. Comisión Europea. European Research Council (ERC) | |
dc.contributor.funder | Comunidad Foral de Navarra (España) | |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | Fundación La Marató TV3 | |
dc.contributor.funder | Fundación ProCNIC | |
dc.contributor.funder | Ministerio de Economía, Industria y Competitividad (España) | |
dc.description.peerreviewed | Sí | |
dc.identifier.e-issn | 1528-0020 | |
dc.relation.publisherversion | https://doi.org/10.1182/blood-2016-08-731166 | |
dc.identifier.journal | Blood | |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Biología de linfocitos B | |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Proteómica cardiovascular | |
dc.repisalud.orgCNIC | CNIC::Unidades técnicas::Proteómica / Metabolómica | |
dc.repisalud.institucion | CNIC | |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2013-45787-R | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SEV-2015-0505 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/713728 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2013-42767-R | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/207844/EU | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/RYC-2009-04503 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/PIE-13-00041 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2010-21394 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/BIO2012-37926 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/BIO2015-67580-P | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/IPT13/0001 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/RD12/0042/00056 | es_ES |
dc.rights.accessRights | open access | es_ES |