MicroRNA-27 enhances differentiation of myeloblasts into granulocytes by post-transcriptionally downregulating Runx1
MicroRNA-27 enhances differentiation of myeloblasts into granulocytes by post-transcriptionally downregulating Runx1
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DOI：
10.1111/j.1365-2141.2009.07632.x
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发表时间：
2009-05-01
影响因子：
6.5
通讯作者：
Kohu, Kazuyoshi
中科院分区：
文献类型：
--
作者：
Feng, Jue;Iwama, Atsushi;Kohu, Kazuyoshi
我们研究了 microRNA (miR)-27 对转录因子 Runx1 的调节及其对成粒细胞分化为粒细胞的影响。当使用粒细胞集落刺激因子 (CSF3) 诱导 32D.cl3 细胞分化时，Runx1 转录适度下调，而 Runx1 蛋白水平完全受到抑制，表明涉及转录后调节。同时，miR-27 及其前体的水平大幅增加。报告基因检测显示 miR-27 靶向 Runx1 转录本的 3'UTR。此外，将 pre-miR-27 单独引入 32D.cl3 细胞会导致 Runx1 蛋白下调，从而即使在不存在 CSF3 的情况下也允许细胞分化。相反，抗miR-27的转导引起Runx1蛋白上调，从而拮抗CSF3介导的粒细胞分化。最后，CSF3 诱导的转录因子 C/EBPα 通过激活其启动子来增强 miR-27 宿主基因 C9orf3 的转录。因此，miR-27 通过转录后下调 Runx1 来增强成髓细胞向粒细胞的分化。
We investigated the regulation of the transcription factor Runx1 by microRNA (miR)-27 and the resulting effects upon the differentiation of myeloblasts into granulocytes. When 32D.cl3 cell differentiation was induced using granulocyte colony-stimulating factor (CSF3), Runx1 transcription was moderately downregulated, while Runx1 protein levels were completely inhibited, suggesting an involvement of post-transcriptional regulation. Simultaneously, levels of miR-27 and its precursor increased substantially. Reporter assays revealed that miR-27 targets the 3'UTR of the Runx1 transcript. Furthermore, introduction of pre-miR-27 alone into 32D.cl3 cells resulted in downregulation of Runx1 protein, thereby allowing the cell differentiation even in the absence of CSF3. Conversely, transduction of anti-miR-27 caused upregulation of Runx1 protein, thereby antagonizing the CSF3-mediated granulocyte differentiation. Finally, the CSF3-induced transcription factor C/EBPalpha enhanced transcription of a host gene of miR-27, C9orf3, via activation of its promoter. Thus, miR-27 enhances differentiation of myeloblasts into granulocytes via post-transcriptional downregulation of Runx1.