Effects of miR‑210‑3p on the erythroid differentiation of K562 cells under hypoxia.

Abstract

GATA binding protein 1 (GATA-1) is one of the most important hematopoietic transcription factors in the production of blood cells, such as platelets, eosinophils, mast cells and erythrocytes. GATA-1 regulates the participation of microRNA (miRNAs/miRs) in erythroid differentiation under normoxia. However, GATA-1 expression and the regulation of miR-210-3p in the context of erythroid differentiation under hypoxia remain unknown. The present study examined the expression levels of GATA-1 and miR-210-3p in the model of erythroid differentiation in K562 cells under hypoxia, and determined the effects of GATA-1, miR-210-3p and SMAD2 on erythroid differentiation through lentivirus transfection experiments. The present study detected increased GATA-1 expression under hypoxia. Moreover, miR-210-3p was identified as a positive regulator of erythroid differentiation, which was upregulated both during erythroid differentiation and in GATA-1 overexpression experiments under hypoxia. Importantly, in the K562 cell model of erythroid differentiation under hypoxia, miR-210-3p was upregulated in a GATA-1-dependent manner. Using a double luciferase reporter assay, miR-210-3p was identified as a downstream target of GATA-1-mediated regulation of erythropoiesis. Gain- or loss-of-function analysis of miR-210-3p identified its importance in erythroid differentiation. Furthermore, it was found that SMAD2 may be a downstream target gene for miR-210-3p. Bioinformatics predictions suggested that SMAD2 mediated miR-210-3p-induced regulation of erythroid differentiation. Collectively, the present study provides novel insights into the miRNA regulation of erythroid differentiation.