Overexpression of miR-669m inhibits erythroblast differentiation
Overexpression of miR-669m inhibits erythroblast differentiation
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DOI：
10.1038/s41598-020-70442-y
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发表时间：
2020-08-11
影响因子：
4.6
通讯作者：
Kotani, Ai
中科院分区：
文献类型：
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作者：
Kotaki, Ryutaro;Kawashima, Masaharu;Kotani, Ai
MicroRNAs （miRNAs）是一种小的非编码rna，通过转录后下调靶基因来调控许多细胞功能。越来越多的研究表明，mirna参与造血过程。在本研究中，我们研究了miR-669m过表达对小鼠体内造血功能的影响，发现miR-669m过表达会抑制红细胞分化。我们的生物信息学分析表明，参与红细胞生成抑制的miR-669m的候选靶点是a激酶锚定蛋白7 （Akap7）和x连锁Kx血型（Xk）基因。这两个基因通过两种不同的计算机方法被预测为miR-669m的靶标，并且在公开的RNA-seq数据中在晚期红母细胞中上调，并通过qPCR证实了这一点。此外，miR-669m抑制了Akap7和Xk基因3 '非翻译区域的荧光素酶报告基因，这支持这些基因是miR-669m的直接靶点。生理上，miR-669m未在红母细胞中表达。总之，利用miR-669m，我们发现了Akap7和Xk，它们可能参与红细胞分化，这意味着操纵这些基因可能是治疗与红细胞功能障碍相关疾病的一种方法。
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.