MicroRNA-22 is induced by vitamin D and contributes to its antiproliferative, antimigratory and gene regulatory effects in colon cancer cells

• Published in: Human molecular genetics Vol. 21; no. 10; pp. 2157 - 2165
• Main Authors: ALVAREZ-DIAZ, Silvia, VALLE, Noelia, FERRER-MAYORGA, Gemma, LOMBARDIA, Luis, HERRERA, Mercedes, DOMINGUEZ, Orlando, SEGURA, Miguel F, BONILLA, Félix, HERNANDO, Eva, MUNOZ, Alberto
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 15.05.2012
• Subjects: Biological and medical sciences; Calcitriol - pharmacology; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms - genetics; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Regulation, Neoplastic; Genetics of eukaryotes. Biological and molecular evolution; HCT116 Cells; Humans; Medical sciences; MicroRNAs - biosynthesis; MicroRNAs - pharmacology; Molecular and cellular biology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Antineoplastic agent; RNA interference; Micro RNA; Malignant tumor; Colonic disease; Gene silencing; Colon cancer; Gene; Vitamin D; Digestive diseases; Intestinal disease; Genetics; Tumor cell; Cancer
• DOI: 10.1093/hmg/dds031
• ISSN: 0964-6906

Vitamin 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 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.