Regulation of human autoimmune regulator (AIRE) gene translation by miR-220b
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- 作者：Tomohito Matsuo ; Yukiko Noguchi ; Mieko Shindo ; Yoshifumi Morita ; Yoshie Oda ; Eiko Yoshida ; Hiroko Hamada ; Mine Harada ; Yuichi Shiokawa ; Takahiro Nishida ; Ryuji Tominaga ; Yoshikane Kikushige ; Koichi Akashi ; Jun Kudoh ; Nobuyoshi Shimizu ; Yuka Tanaka ; Tsukuru Umemura ; Taketoshi Taniguchi ; Akihiko Yoshimura ; Takashi Kobayashi ; et al.
- 关键词：AIRE ; autoimmune regulator ; APECED ; autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy ; APS-1 ; autoimmune polyglandular syndrome type 1 ; EBV-B ; Epstein&ndash ; Barr virus transformed B ; IL-2T ; antigen and IL-2-stimulated CD4+ T ; OTC-4-AIRE ; OTC-
- 刊名：Gene
- 出版年：2013
- 出版时间：1 November, 2013
- 年：2013
- 卷：530
- 期：1
- 页码：19-25
- 全文大小：703 K
文摘
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¡äUTR 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¡äUTR region transfected cells. Moreover, when AIRE gene transfected cells with mutated 3¡äUTR 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¡äUTR region of AIRE gene, indicating that miR-220b could serve as a regulator for human AIRE gene translation.