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Gene. 2013 Nov 1;530(1):19-25. doi: 10.1016/j.gene.2013.08.015. Epub 2013 Aug 14.

Regulation of human autoimmune regulator (AIRE) gene translation by miR-220b.

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  • 1Department of Medical Science and Technology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.

Abstract

Although mutations of autoimmune regulator (AIRE) gene are responsible for autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), presenting a wide spectrum of many characteristic and non-characteristic clinical features, some patients lack AIRE gene mutations. Therefore, something other than a mutation, such as dysregulation of AIRE gene, may be a causal factor for APECED or its related diseases. However, regulatory mechanisms for AIRE gene expression and/or translation have still remained elusive. We found that IL-2-stimulated CD4(+) T (IL-2T) cells showed a high expression of AIRE gene, but very low AIRE protein production, while Epstein-Barr virus-transformed B (EBV-B) cells express both AIRE gene and AIRE protein. By using microarray analysis, we could identify miR-220b as a possible regulatory mechanism for AIRE gene translation in IL-2T cells. Here we report that miR-220b significantly reduced the expression of AIRE protein in AIRE gene with 3'UTR region transfected 293T cells, whereas no alteration of AIRE protein production was observed in the open reading frame of AIRE gene alone transfected cells. In addition, anti-miR-220b reversed the inhibitory function of miR-220b for the expression of AIRE protein in AIRE gene with 3'UTR region transfected cells. Moreover, when AIRE gene transfected cells with mutated 3'UTR were transfected with miR-220b, no reduction of AIRE protein production was observed. Taken together, it was concluded that miR-220b inhibited the AIRE gene translation through the 3'UTR region of AIRE gene, indicating that miR-220b could serve as a regulator for human AIRE gene translation.

KEYWORDS:

AIRE; APECED; APS-1; Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy; Autoimmune regulator gene; EBV-B; Epstein–Barr virus transformed B; IL-2T; MicroRNA; OTC-4 cells transfected with AIRE cDNA; OTC-4-AIRE; Translation; antigen and IL-2-stimulated CD4(+) T; autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy; autoimmune polyglandular syndrome type 1; autoimmune regulator

PMID:
23954874
DOI:
10.1016/j.gene.2013.08.015
[PubMed - indexed for MEDLINE]
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