miR-17-3p的上调与β地中海贫血患者的胎儿血红蛋白（HbF）相关，并通过靶向BCL11A诱导γ珠蛋白表达。
Upregulation of miR-17-3p is associated with HbF in patients with β-thalassemia and induces γ-globin expression by targeting BCL11A.
作者信息
Zhang Siwen, Chen Meihuan, Zhao Wantong, Zheng Junhao, Zhang Yanhong, Lv Aixiang, Li Jingmin, Cao Hua, Xu Liangpu, Huang Hailong
机构信息
Medical Genetic Diagnosis and Therapy Center of Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fujian Provincial Key Laboratory of Prenatal Diagnosis and Birth Defect, No. 18 Daoshan Road, Gulou District, Fuzhou, Fujian, 350001, China.
The School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, China.
出版信息
Orphanet J Rare Dis. 2025 May 30;20(1):260. doi: 10.1186/s13023-025-03806-0.
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.
背景
已发现大量微小RNA（miRNA）在β地中海贫血中表达失调，但其在β地中海贫血中的作用报道较少。本研究旨在探讨miR-17-3p在β地中海贫血中的临床意义，并阐明其对红细胞生成和γ珠蛋白表达的调控作用。
方法
我们收集了17例β地中海贫血患者（包括中间型和重型亚型）及17例健康对照者的外周血样本，采用qRT-PCR检测miR-17-3p、BCL11转录因子A（BCL11A）和γ珠蛋白的表达水平，并分析它们之间的相关性。通过生物信息学、荧光素酶报告基因检测、荧光原位杂交和蛋白质印迹法在K562细胞中评估miR-17-3p对BCL11A的调控作用。此外，通过CCK-8、流式细胞术和联苯胺蓝染色评估miR-17-3p过表达和敲低对K562细胞红细胞生成的影响，包括细胞增殖、细胞周期、细胞凋亡和红系分化。
结果
β地中海贫血患者中miR-17-3p表达上调，且与胎儿血红蛋白（HbF）水平呈正相关。β地中海贫血患者中BCL11A表达降低，且与miR-亦与γ珠蛋白表达呈负相关。BCL11A被鉴定为miR-17-3p的靶基因，并受到miR-17-3p的负调控。此外，miR-17-3p通过BCL11A介导K562细胞中γ珠蛋白表达的上调。此外，miR-17-3p的过表达和敲低在体外均未影响K562细胞的细胞增殖、细胞周期、细胞凋亡或红系分化。
结论
β地中海贫血患者中miR-17-3p上调与HbF相关。虽然miR-17-3p不影响红细胞生成，但它通过靶向BCL11A促进γ珠蛋白表达，提示miR-17-3p可能是治疗β地中海贫血的一种有前景的miRNA。
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