MicroRNA-92a-3p-mediated Inhibition Of BCL11A Upregulates γ-globin Expression And Inhibits Oxidative Stress And Apoptosis In Erythroid Precursor Cells

ObjectiveThis study attempted to investigate miR-92a-3p expression in peripheral blood of patients with severe β-thalassemia,and the effect and action mechanism of miR-92a3p on γ-globin expression and oxidative stress in erythroid precursor cells.MethodsCD34+hematopoietic progenitor cells(HPCs)were isolated from mobilization of peripheral blood of healthy volunteers and patients with severe β-thalassemia.The levels of miR-92a-3p,BCL11A,and γ-globin were measured in erythroid precursor cells.High-performance liquid chromatography(HPLC)was used to analyze hemoglobin F(HbF)content.HPCs were induced with erythroid differentiation and erythroid precursor cells were then obtained.The relevance between miR-92a-3p and BCL11A was studied using dual luciferase reporter gene assay,and the correlation between miR-92a-3p and HbF was assayed by Pearson correlation analysis.Reactive oxygen species(ROS),glutathione(GSH),malondialdehyde(MDA),and superoxide dismutase(SOD)in erythroid precursor cells were tested to evaluate oxidative stress.Cell apoptosis was examined by flow cytometry.ResultsRemarkably higher expression of miR-92a-3p was observed in erythroid precursor cells.Increased expression of miR-92a-3p resulted in elevated levels of γ-globin,GSH,and SOD,reduced expression of ROS and MDA,and decreased cell apoptosis.BCL11A was identified as a target of miR-92a-3p and to be downregulated by miR92a-3p.Moreover,BCL11A knockdown alone increased the expression of γ-globin,SOD and GSH,and repressed the levels of ROS and MDA and cell apoptosis,and the following inhibition of miR-92a-3p changed these patterns.ConclusionsOur data indicated that miR-92a-3p might increase γ-globin level and reduce oxidative stress and apoptosis in erythroid precursor cells by downregulating BCL11A.