期刊
HUMAN MOLECULAR GENETICS
卷 21, 期 10, 页码 2157-2165出版社
OXFORD UNIV PRESS
DOI: 10.1093/hmg/dds031
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资金
- Ministerio de Ciencia e Innovacion of Spain [SAF2010-18302]
- Comunidad de Madrid [S2011/BMD-2344]
- Fondo Europeo de Desarrollo Regional-Instituto de Salud Carlos III [RD06/0020/0009, RD06/0020/0020]
Vitamin D deficiency is associated with the high risk of colon cancer and a variety of other diseases. The active vitamin D metabolite 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) 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)(2)D-3 targets in human colon cancer cells. Remarkably, miR-22 is induced by 1,25(OH)(2)D-3 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)(2)D-3. Additionally, miR-22 inhibition increases cell migration per se and decreases the antimigratory effect of 1,25(OH)(2)D-3 in both cell types. In silico analysis shows a significant overlap between genes suppressed by 1,25(OH)(2)D-3 and miR-22 putative target genes. Consistently, miR-22 inhibition abrogates the 1,25(OH)(2)D-3-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)(2)D-3 in human colon cancer cells and it may contribute to its antitumour action against this neoplasia.
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