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dc.contributor.authorTorres, Sofíaes_ES
dc.contributor.authorGarcía-Palmero, Irenees_ES
dc.contributor.authorBartolomé, Rubén Álvaroes_ES
dc.contributor.authorFernandez-Aceñero, M. Jesúses_ES
dc.contributor.authorMolina, Elenaes_ES
dc.contributor.authorCalviño, Evaes_ES
dc.contributor.authorSegura, Miguel F.es_ES
dc.contributor.authorCasal, J. Ignacioes_ES
dc.date.accessioned2017-04-07T12:03:07Z-
dc.date.available2017-04-07T12:03:07Z-
dc.date.issued2017-03-07-
dc.identifier.citationThe Journal of Pathology (2017)es_ES
dc.identifier.issn0022-3417-
dc.identifier.urihttp://hdl.handle.net/10261/148144-
dc.description39 p.-6 fig.es_ES
dc.description.abstractThe process of liver colonization in colorectal cancer remains poorly characterized. Here, we addressed the role of microRNA (miRNA) dysregulation in metastasis. We first compared miRNA expression profiles between colorectal cancer cell lines with different metastatic properties and then identified target proteins of the dysregulated miRNAs to establish their functions and prognostic value. We found that 38 miRNAs were differentially expressed between highly metastatic (KM12SM/SW620) and poorly metastatic (KM12C/SW480) cancer cell lines. After initial validation, we determined that three miRNAs (miR-424-3p, −503, and −1292) were overexpressed in metastatic colorectal cancer cell lines and human samples. Stable transduction of non-metastatic cells with each of the three miRNAs promoted metastatic properties in culture and increased liver colonization in vivo. Moreover, miR-424-3p and miR-1292 were associated with poor prognosis in human patients. A quantitative proteomic analysis of colorectal cancer cells transfected with miR-424-3p, miR-503, or miR-1292 identified alterations in 149, 129, or 121 proteins, respectively, with an extensive overlap of the target proteins of the three miRNAs. Importantly, down-regulation of two of these shared target proteins, CKB and UBA2, increased cell adhesion and proliferation in colorectal cancer cells. The capacity of distinct miRNAs to regulate the same mRNAs boosts the capacity of miRNAs to regulate cancer metastasis and underscores the necessity of targeting multiple miRNAs for effective cancer therapy. Copyright © 2017 Pathological Society of Great Britain and Ireland.es_ES
dc.description.sponsorshipThis research was supported by grants BIO2012-31023 and BIO2015-66489-R from MINECO, and PRB2 (IPT13/0001-ISCIII-SGEFI/FEDER) from the Instituto de Salud Carlos III-FEDER.es_ES
dc.language.isoenges_ES
dc.publisherJohn Wiley & Sonses_ES
dc.relation.isversionofPostprintes_ES
dc.rightsopenAccessen_EN
dc.subjectMetastasises_ES
dc.subjectColorectal canceres_ES
dc.subjectmiR-424-3pes_ES
dc.subjectmiR-503es_ES
dc.subjectmiR-1292es_ES
dc.subjectCKBes_ES
dc.subjectUBA2es_ES
dc.titleCombined miRNA profiling and proteomics demonstrates that different miRNAs target a common set of proteins to promote colorectal cancer metastasises_ES
dc.title.alternativemiRNAs in colorectal cancer metastasises_ES
dc.typeartículoes_ES
dc.identifier.doi10.1002/path.4874-
dc.description.peerreviewedPeer reviewedes_ES
dc.relation.publisherversionhttp://dx.doi.org/10.1002/path.4874es_ES
dc.identifier.e-issn1096-9896-
dc.embargo.terms2018-03-07es_ES
dc.contributor.funderMinisterio de Economía y Competitividad (España)es_ES
dc.contributor.funderInstituto de Salud Carlos IIIes_ES
dc.relation.csices_ES
oprm.item.hasRevisionno ko 0 false*
dc.identifier.funderhttp://dx.doi.org/10.13039/501100003329es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100004587es_ES
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