title: A comprehensive analysis of GATA-1-regulated miRNAs reveals miR-23a to be a positive modulator of erythropoiesis.
abstract: miRNAs play important roles in many biological processes, including erythropoiesis. Although several miRNAs regulate erythroid differentiation, how the key erythroid regulator, GATA-1, directly orchestrates differentiation through miRNA pathways remains unclear. In this study, we identified miR-23a as a key regulator of erythropoiesis, which was upregulated both during erythroid differentiation and in GATA-1 gain-of-function experiments, as determined by miRNA expression profile analysis. In primary human CD34+ hematopoietic progenitor cells, miR-23a increased in a GATA-1-dependent manner during erythroid differentiation. Gain- or loss-of-function analysis of miR-23a in mice or zebrafish demonstrated that it was essential for normal morphology in terminally differentiated erythroid cells. Furthermore, a protein tyrosine phosphatase, SHP2, was identified as a downstream target of miR-23a that mediated its regulation of erythropoiesis. Taken together, our data identify a key GATA-1-miRNA axis in erythroid differentiation.
authors: National Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing 100005, PR China.
authors: Yong
authors: Y
authors: Zhu
authors: Dongsheng
authors: D
authors: Wang
authors: Fang
authors: F
authors: Wang
authors: Tingting
authors: T
authors: Li
authors: Lei
authors: L
authors: Dong
authors: Huiwen
authors: H
authors: Liu
authors: Yanni
authors: Y
authors: Ma
authors: Fengbing
authors: F
authors: Jiang
authors: Haixin
authors: H
authors: Yin
authors: Wenting
authors: W
authors: Yan
authors: Min
authors: M
authors: Luo
authors: Zhong
authors: Z
authors: Tang
authors: Guoyuan
authors: G
authors: Zhang
authors: Qiang
authors: Q
authors: Wang
authors: Junwu
authors: J
authors: Zhang
authors: Jingguo
authors: J
authors: Zhou
authors: Jia
authors: J
authors: Yu
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D041905:Erythroid Cells / Q000166:cytology; D004920:Erythropoiesis / Q000235:genetics*; D050982:GATA1 Transcription Factor / Q000378:metabolism*; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis / Q000378:metabolism*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics; D015533:Transcriptional Activation; D015027:Zebrafish / Q000235:genetics
chemical_list: D050982:GATA1 Transcription Factor; C552430:MIRN23a microRNA, human; D035683:MicroRNAs; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11