微小RNA对β-地中海贫血中γ-珠蛋白基因的调控机制研究进展

The regulatory mechanism of microRNAs onγ-globin gene inβ-thalassemia

β-地中海贫血(β-地贫)是β-珠蛋白基因发生突变导致β-珠蛋白合成减少或缺如,以溶血性贫血为主要临床特征的一类单基因遗传病。目前暂无治疗该病的特效药。研究已证实,一些转录因子通过调控γ-珠蛋白基因增加胎儿血红蛋白表达,从而缓解无效造血,改善β-地贫患者的临床症状,降低对输血依赖性。随着表观遗传学研究的不断深入,发现微小RNA(microRNA,miRNA)不仅在β-地贫患者中存在表达失衡,也参与γ-珠蛋白基因的转录调控。全面了解miRNA对γ-珠蛋白基因的调控作用能够为阐明β-地贫的致病机制并对该病的精准治疗提供新的思路和方向。

β-thalassemia(β-thal)is a single-gene inheritance disease and hemolytic anemia is the main symptom due to the decrease or absence ofβ-globin synthesis after mutation ofβ-globin gene.Currently,there is no specific medi‐cine for the treatment ofβ-thal.However,there were studies showed that some transcription factors can increase the ex‐pression of fetal hemoglobin by regulatingγ-globin gene,and thereby alleviated the ineffective hematopoiesis and im‐proved the clinical symptoms ofβ-thal patients and reduced the dependence on blood transfusion.With the accumula‐tion of epigenetic studies,it was found that microRNAs(miRNAs)were dysregulated in patients withβ-thal and partici‐pated in the transcriptional regulation ofγ-globin gene.A comprehensive understanding of the regulatory effect of miR‐NA on theγ-globin gene can provide new ideas and directions for elucidating the pathogenic mechanism ofβ-thal and precise treatment of the disease.Therefore,this article reviews the regulatory mechanism of miRNA onγ-globin gene.