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dc.contributor.authorCristóbal, Ion
dc.contributor.authorCaramés, Cristina
dc.contributor.authorRincón, Raúl
dc.contributor.authorManso, Rebeca
dc.contributor.authorMadoz-Gúrpide, Juan
dc.contributor.authorTorrejón, Blanca
dc.contributor.authorGonzález-Alonso, Paula
dc.contributor.authorRojo, Federico
dc.contributor.authorGarcía-Foncillas López, Jesús Miguel 
dc.contributor.otherUAM. Departamento de Medicinaes_ES
dc.contributor.otherInstituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD)es_ES
dc.date.accessioned2017-11-14T16:07:29Z
dc.date.available2017-11-14T16:07:29Z
dc.date.issued2016-08-10
dc.identifier.citationOncotarget 8.25 (2017): 40169-40180en_US
dc.identifier.issn1949-2553es_ES
dc.identifier.urihttp://hdl.handle.net/10486/680230
dc.description.abstractThe tumor suppressor microRNA-199b (miR-199b) is a negative SET regulator associated with poor outcome in some human cancers. However, its expression levels as well as potential biological and clinical significance in colorectal cancer (CRC) remain completely unexplored. The PP2A inhibitor SET has shown promising therapeutic and clinical implications in metastatic CRC (mCRC) but the molecular mechanisms underlying SET deregulation are currently unknown. We show here miR-199b downregulation in 4 out of 5 CRC SET-overexpressing cell lines and its inverse correlation with SET overexpression in CRC patients. Moreover, miR-199b led to PP2A activation through a direct SET inhibition, impaired cell viability and enhanced oxaliplatin sensitivity in CRC cells. MiR-199b was found downregulated in 25% of cases, and associated with lymph metastasis (p = 0.049), presence of synchronous metastasis at diagnosis (p = 0.026) and SET overexpression (p < 0.001). Furthermore, low miR-199b levels determined shorter overall (p < 0.001), progression-free survival (p = 0.003) and predicted clinical benefit to oxaliplatin treatment. The miR-199b prognostic impact was particularly evident in both younger and KRAS wild-type subgroups. Multivariate analyses confirmed its independent prognostic impact. Altogether, our results show that miR-199b is a tumor suppressor whose downregulation independently determines worse outcome and emerges as a potential contributing mechanism to inhibit PP2A via SET overexpression in a subgroup of mCRC patientsen_US
dc.format.extent12 pag.es_ES
dc.format.mimetypeapplication/pdfen
dc.language.isoengen
dc.publisherImpact Journals LLCen_US
dc.relation.ispartofOncotargeten_US
dc.rights© Cristóbal et al.es_ES
dc.subject.otherMicroRNA-199ben_US
dc.subject.otherColorectal canceren_US
dc.subject.otherPP2A inhibitoren_US
dc.subject.otherMetastaticen_US
dc.subject.otherInhibitiones_ES
dc.subject.otherDownregulationen_US
dc.titleDownregulation of microRNA-199b predicts unfavorable prognosis and emerges as a novel therapeutic target which contributes to PP2A inhibition in metastatic colorectal canceren_US
dc.typearticleen
dc.subject.ecienciaMedicinaes_ES
dc.relation.publisherversionhttps://doi.org/10.18632/oncotarget.11174
dc.identifier.doi10.18632/oncotarget.11174
dc.identifier.publicationfirstpage40169es_ES
dc.identifier.publicationissue25es_ES
dc.identifier.publicationlastpage40180es_ES
dc.identifier.publicationvolume8es_ES
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
dc.rights.ccReconocimientoes_ES
dc.rights.accessRightsopenAccesses_ES
dc.facultadUAMFacultad de Medicina
dc.institutoUAMInstituto de Investigación Sanitaria Fundación Jiménez Díaz (ISS-FJD)


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