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dc.contributor.authorÁlvarez-Díaz, S.-
dc.contributor.authorValle, Noelia-
dc.contributor.authorFerrer-Mayorga, Gemma-
dc.contributor.authorLombardía, Luis-
dc.contributor.authorHerrera, Mercedes-
dc.contributor.authorDomínguez, Orlando-
dc.contributor.authorSegura, Miguel F.-
dc.contributor.authorBonilla, Félix-
dc.contributor.authorHernando, Eva-
dc.contributor.authorMuñoz Terol, Alberto-
dc.identifier.citationHuman Molecular Genetics 21(10): 2157-2165 (2012)es_ES
dc.descriptionThis is a pre-copy-editing, author-produced PDF of an article accepted for publication in Human Molecular Genetics following peer review.-
dc.description.abstractVitamin D deficiency is associated with the high risk of colon cancer and a variety of other diseases. The active vitamin D metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) regulates gene transcription via its nuclear receptor (VDR), and posttranscriptional regulatory mechanisms of gene expression have also been proposed. We have identified microRNA-22 (miR-22) and several other miRNA species as 1,25(OH)2D3 targets in human colon cancer cells. Remarkably, miR-22 is induced by 1,25(OH)2D3 in a time-, dose- and VDR-dependent manner. In SW480-ADH and HCT116 cells, miR-22 loss-of-function by transfection of a miR-22 inhibitor suppresses the antiproliferative effect of 1,25(OH)2D3. Additionally, miR-22 inhibition increases cell migration per se and decreases the antimigratory effect of 1,25(OH)2D3 in both cell types. In silico analysis shows a significant overlap between genes suppressed by 1,25(OH)2D3 and miR-22 putative target genes. Consistently, miR-22 inhibition abrogates the 1,25(OH)2D3-mediated suppression of NELL2, OGN, HNRPH1, RERE and NFAT5 genes. In 39 out of 50 (78%) human colon cancer patients, miR-22 expression was found lower in the tumour than in the matched normal tissue and correlated directly with that of VDR. Our results indicate that miR-22 is induced by 1,25(OH)2D3 in human colon cancer cells and it may contribute to its antitumour action against this neoplasia.es_ES
dc.description.sponsorshipThis work was supported by the Ministerio de Ciencia e Innovación of Spain (SAF2010-18302), Comunidad de Madrid (Colomics2, S2011/BMD-2344) and Fondo Europeo de Desarrollo Regional-Instituto de Salud Carlos III (RD06/0020/0009 to A.M. and RD06/0020/0020 to F.B.).es_ES
dc.publisherOxford University Presses_ES
dc.titleMicroRNA-22 is induced by vitamin D and contributes to its antiproliferative, antimigratory and gene regulatory effects in colon cancer cellses_ES
dc.description.peerreviewedPeer reviewedes_ES
dc.contributor.funderMinisterio de Ciencia e Innovación (España)-
dc.contributor.funderComunidad de Madrid-
dc.contributor.funderInstituto de Salud Carlos III-
dc.contributor.funderEuropean Commission-
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