Upregulation of miR-17-3p is associated with HbF in patients with β-thalassemia and induces γ-globin expression by targeting BCL11A.

Background: Large number of microRNAs (miRNAs) have been found to be dysregulated in β-thalassemia, but their roles in β-thalassemia are poorly reported. This study aims to investigate the clinical significance of miR-17-3p in β-thalassemia, and to elucidate its regulatory effect on erythropoiesis and γ-globin expression.

Methods: We collected peripheral blood samples from 17 patients with β-thalassemia (including intermedia and major subtypes) and 17 healthy controls, and the expression levels of miR-17-3p, BCL11 transcription factor A (BCL11A) and γ-globin were detected by qRT-PCR, and their correlations were analyzed. The regulation of miR-17-3p on BCL11A was evaluated in K562 cells by bioinformatics, luciferase reporter gene assay, fluorescence in situ hybridization and Western blotting. Furthermore, the effects on miR-17-3p overexpression and knockdown on erythropoiesis including cell proliferation, cell cycle, cell apoptosis, and erythroid differentiation of K562 cells were assessed by CCK-8, flow cytometry and benzidine blue staining.

Results: The expression of miR-17-3p was upregulated in patients with β-thalassemia, and was positively correlated with fetal hemoglobin (HbF) levels. BCL11A expression was reduced in β-thalassemia patients, and was negatively correlated with miR-17-3p and γ-globin expression. BCL11A was identified as a target gene of miR-17-3p, and was negatively regulated by miR-17-3p. Furthermore, miR-17-3p mediated the upregulation of γ-globin expression in K562 cells through BCL11A. In addition, neither overexpression nor knockdown of miR-17-3p appeared to affect cell proliferation, cell cycle, cell apoptosis or erythroid differentiation of K562 cells in vitro.

Conclusion: The upregulated miR-17-3p is associated with HbF in patients with β-thalassemia. Although miR-17-3p does not affect erythropoiesis, it promotes γ-globin expression by targeting BCL11A, suggesting that miR-17-3p may be a promising miRNA for the treatment of β-thalassemia.