Clinical Medical College, Yangzhou University, Yangzhou, China; Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Yangzhou University Medical College, Yangzhou, China.
Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Yangzhou University Medical College, Yangzhou, China.
Am J Med Sci. 2021 Jul;362(1):5-12. doi: 10.1016/j.amjms.2021.02.011. Epub 2021 Feb 16.
β-thalassemia is a lethal inherited disease resulting from β-globin gene mutations. Severe β-thalassemia requires regular blood transfusions. Other active interventions, including iron chelating, stem cell transplantation and gene therapy, have remarkably improved the quality of life and prolonged the survival of patients with transfusion-dependent β-thalassemia, but all with significant limitations and complications. MicroRNAs (miRNAs), encoded by a class of endogenous genes, are found to play important roles in regulating globin expression. Among the miRNAs of particular interest related to β-thalassemia, miR-15a/16-1, miR-486-3p, miR-26b, miR-199b-5p, miR-210, miR-34a, miR-138, miR-326, let-7, and miR-17/92 cluster elevate γ-globin expression, while miR-96, miR-146a, miR-223-3p, and miR-144 inhibit γ-globin expression. A couple of miRNAs, miR-144 and miR-150, repress α-globin expression, whereas miR-451 induces α-, β- and γ-globin expression. Single nucleotide polymorphism in miRNA genes or their targeted genes might also contribute to the abnormal expression of hemoglobin. Moreover, changes in the expression of miR-125b, miR-210, miR-451, and miR-609 reflect the severity of anemia and hemolysis in β-thalassemia patients. These results suggest that miRNAs are potential biomarkers for the diagnosis and prognosis of β-thalassemia, and miRNA-based therapeutic strategy might be used as a coordinated approach for effectively treating β-thalassemia.
β-地中海贫血是一种致命的遗传性疾病，由β-珠蛋白基因突变引起。严重的β-地中海贫血需要定期输血。其他积极的干预措施，包括铁螯合、干细胞移植和基因治疗，显著改善了依赖输血的β-地中海贫血患者的生活质量和延长了患者的生存时间，但都存在显著的局限性和并发症。微小 RNA（miRNA）是一类内源性基因编码的，在调节珠蛋白表达中发挥重要作用。在与β-地中海贫血相关的特别感兴趣的 miRNA 中，miR-15a/16-1、miR-486-3p、miR-26b、miR-199b-5p、miR-210、miR-34a、miR-138、miR-326、let-7 和 miR-17/92 簇升高 γ-珠蛋白表达，而 miR-96、miR-146a、miR-223-3p 和 miR-144 抑制 γ-珠蛋白表达。一些 miRNA，如 miR-144 和 miR-150，抑制 α-珠蛋白表达，而 miR-451 诱导 α-、β-和 γ-珠蛋白表达。miRNA 基因或其靶向基因的单核苷酸多态性也可能导致血红蛋白表达异常。此外，miR-125b、miR-210、miR-451 和 miR-609 的表达变化反映了β-地中海贫血患者贫血和溶血的严重程度。这些结果表明，miRNA 是β-地中海贫血诊断和预后的潜在生物标志物，基于 miRNA 的治疗策略可能作为一种有效的协同方法用于治疗β-地中海贫血。
