Overexpression of miR-669m inhibits erythroblast differentiation

miR-669m 过度表达抑制红细胞分化

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作者:Ryutaro Kotaki #, Masaharu Kawashima #, Asuka Yamaguchi #, Naoto Suzuki #, Ryo Koyama-Nasu, Daisuke Ogiya, Kazuki Okuyama, Yuichiro Yamamoto, Masako Takamatsu, Natsumi Kurosaki, Kiyoshi Ando, Akihiko Murata, Masato Ohtsuka, So Nakagawa, Koko Katagiri, Ai Kotani

Abstract

MicroRNAs (miRNAs), one of small non-coding RNAs, regulate many cell functions through their post-transcriptionally downregulation of target genes. Accumulated studies have revealed that miRNAs are involved in hematopoiesis. In the present study, we investigated effects of miR-669m overexpression on hematopoiesis in mouse in vivo, and found that erythroid differentiation was inhibited by the overexpression. Our bioinformatic analyses showed that candidate targets of miR-669m which are involved in the erythropoiesis inhibition are A-kinase anchoring protein 7 (Akap7) and X-linked Kx blood group (Xk) genes. These two genes were predicted as targets of miR-669m by two different in silico methods and were upregulated in late erythroblasts in a public RNA-seq data, which was confirmed with qPCR. Further, miR-669m suppressed luciferase reporters for 3' untranslated regions of Akap7 and Xk genes, which supports these genes are direct targets of miR-669m. Physiologically, miR-669m was not expressed in the erythroblast. In conclusion, using miR-669m, we found Akap7 and Xk, which may be involved in erythroid differentiation, implying that manipulating these genes could be a therapeutic way for diseases associated with erythropoiesis dysfunction.

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