The up-regulation of miR-199b-5p in erythroid differentiation is associated with GATA-1 and NF-E2.
The up-regulation of miR-199b-5p in erythroid differentiation is associated with GATA-1 and NF-E2.
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DOI：
10.14348/molcells.2014.2288
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发表时间：
2014-03
影响因子：
3.8
通讯作者：
Wang F
中科院分区：
文献类型：
--
作者：
Li Y;Bai H;Zhang Z;Li W;Dong L;Wei X;Ma Y;Zhang J;Yu J;Sun G;Wang F
MicroRNAs(MiRNAs)是一类非编码的小分子调控RNA，在包括红细胞生成在内的正常造血过程中发挥重要作用。尽管研究已经确定了几个调节红系承诺和分化的miRNAs，但我们还不清楚关键的红系转录因子GATA-1和NF-E2通过miRNA途径直接调控分化的机制。在本研究中，我们发现miR-199B-5P是人红细胞生成的关键调节因子，并且在K562细胞的红系分化过程中其表达上调。此外，在红细胞成熟过程中，miR-199B-5p在红系细胞中的表达增加依赖于GATA-1和NF-E_2。GATA-1和NF-E2都结合在miR-199B基因的上游，并激活其转录。在K562细胞中强制表达miRNA-199B-5p会影响红系细胞的增殖和成熟。此外，我们还发现c-Kit是miR-199B-5p在红系细胞中的直接靶点。综上所述，我们的结果建立了红系转录因子GATA-1/NF-E2、miR-199B-5p和c-Kit之间的功能联系，并为红系分化中转录和转录后调控的耦合提供了新的见解。
MicroRNAs (miRNAs) represent a class of small non-coding regulatory RNAs that play important roles in normal hematopoiesis, including erythropoiesis. Although studies have identified several miRNAs that regulate erythroid commitment and differentiation, we do not understand the mechanism by which the crucial erythroid transcription factors, GATA-1and NF-E2 directly regulate and control differentiation via miRNA pathways. In this study, we identified miR-199b-5p as a key regulator of human erythropoiesis, and its expression was up-regulated during the erythroid differentiation of K562 cells. Furthermore, the increase of miR-199b-5p in erythroid cells occurred in a GATA-1- and NF-E2-dependent manner during erythrocyte maturation. Both GATA-1 and NF-E2 bound upstream of the miR-199b gene locus and activated its transcription. Forced expression of miRNA-199b-5p in K562 cells affected erythroid cell proliferation and maturation. Moreover, we identified c-Kit as a direct target of miR-199b-5p in erythroid cells. Taken together, our results establish a functional link among the erythroid transcription factors GATA-1/NF-E2, miR-199b-5p and c-Kit, and provide new insights into the coupling of transcription and post-transcription regulation in erythroid differentiation.