MicroRNA-92a-3p-mediated inhibition of BCL11A upregulates γ-globin expression and inhibits oxidative stress and apoptosis in erythroid precursor cells

ABSTRACT

Objective

This 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-92a-3p on γ-globin expression and oxidative stress in erythroid precursor cells.

Methods

CD34⁺ hematopoietic progenitor cells (HPCs) were isolated from 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.

Results

Remarkably 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 miR-92a-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.

Conclusions

Our data indicated that miR-92a-3p might increase γ-globin level and reduce oxidative stress and apoptosis in erythroid precursor cells by downregulating BCL11A.

KEYWORDS:

• MicroRNA-92a-3p
• BCL11A
• γ-globin
• severe β-thalassemia
• oxidative stress

Acknowledgement

The instructor has strict requirements for the topic selection, writing, and final draft of the thesis. Without the efforts and guidance of the instructor, this paper would not be finished, and my results could not have been achieved. The rigorous attitude of the instructor towards academics deeply touched me. On this occasion, I would like to express my gratitude to my instructor. I will always remember the instructor's sincere teachings. At the same time, during this process, I made many lovely friends who have helped me a lot academically and will be my partners along the way in the future.

Disclosure statement

No potential conflict of interest was reported by the author(s).