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http://dx.doi.org/10.14348/molcells.2014.2288

The Up-Regulation of miR-199b-5p in Erythroid Differentiation Is Associated with GATA-1 and NF-E2  

Li, Yuxia (Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), National Laboratory of Medical Molecular Biology)
Bai, Hua (Department of Ophthalmology, The Military General Hospitalof Beijing PLA)
Zhang, Zhongzu (Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), National Laboratory of Medical Molecular Biology)
li, Weihua (Henan University Hospital of Huaihe Henan University Clinical College KaiFeng)
Dong, Lei (Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), National Laboratory of Medical Molecular Biology)
Wei, Xueju (Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), National Laboratory of Medical Molecular Biology)
Ma, Yanni (Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), National Laboratory of Medical Molecular Biology)
Zhang, Junwu (Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), National Laboratory of Medical Molecular Biology)
Yu, Jia (Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), National Laboratory of Medical Molecular Biology)
Sun, Guotao (Institute of Molecular Medicine, Medical School, Henan University)
Wang, Fang (Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), National Laboratory of Medical Molecular Biology)
Abstract
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.
Keywords
c-Kit; erythroid differentiation; GATA-1; microRNA-199b-5p; NF-E2;
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