A comprehensive analysis of GATA-1-regulated miRNAs reveals miR-23a to be a positive modulator of erythropoiesis
- Authors
- Zhu, Y., 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., and Yu, J.
- ID
- ZDB-PUB-130308-25
- Date
- 2013
- Source
- Nucleic acids research 41(7): 4129-43 (Journal)
- Registered Authors
- Wang, Fang, Zhu, Yong
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Differentiation
- Cells, Cultured
- Erythroid Cells/cytology
- Erythropoiesis/genetics*
- GATA1 Transcription Factor/metabolism*
- Gene Expression Profiling
- Hematopoietic Stem Cells/cytology
- Hematopoietic Stem Cells/metabolism
- Humans
- K562 Cells
- Mice
- MicroRNAs/biosynthesis
- MicroRNAs/metabolism*
- Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics
- Transcriptional Activation
- Zebrafish/genetics
- PubMed
- 23420868 Full text @ Nucleic Acids Res.
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.