A comprehensive analysis of GATA-1-regulated miRNAs reveals miR-23a to be a positive modulator of erythropoiesis.
Nucleic Acids Res, 2013/4;41(7):4129-43.
Zhu Y[1], Wang D, Wang F, Li T, Dong L, Liu H, Ma Y, Jiang F, Yin H, Yan W, Luo M, Tang Z, Zhang G, Wang Q, Zhang J, Zhou J, Yu J
Affiliations
PMID: 23420868DOI: 10.1093/nar/gkt093
Impact factor: 19.16
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.
MeSH terms
Animals; Cell Differentiation; Cells, Cultured; Erythroid Cells; Erythropoiesis; GATA1 Transcription Factor; Gene Expression Profiling; Hematopoietic Stem Cells; Humans; K562 Cells; Mice; MicroRNAs; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Transcriptional Activation; Zebrafish
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