Upregulation of miR-17-3p is associated with HbF in patients with β-thalassemia and induces γ-globin expression by targeting BCL11A
Abstract 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 erythrop...
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BMC
2025-05-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | https://doi.org/10.1186/s13023-025-03806-0 |
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| author | Siwen Zhang Meihuan Chen Wantong Zhao Junhao Zheng Yanhong Zhang Aixiang Lv Jingmin Li Hua Cao Liangpu Xu Hailong Huang |
| author_facet | Siwen Zhang Meihuan Chen Wantong Zhao Junhao Zheng Yanhong Zhang Aixiang Lv Jingmin Li Hua Cao Liangpu Xu Hailong Huang |
| author_sort | Siwen Zhang |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-512fa0da726946d9b48b9f2417d8ea18 |
| institution | DOAJ |
| issn | 1750-1172 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
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| series | Orphanet Journal of Rare Diseases |
| spelling | doaj-art-512fa0da726946d9b48b9f2417d8ea182025-08-20T03:22:08ZengBMCOrphanet Journal of Rare Diseases1750-11722025-05-0120111310.1186/s13023-025-03806-0Upregulation of miR-17-3p is associated with HbF in patients with β-thalassemia and induces γ-globin expression by targeting BCL11ASiwen Zhang0Meihuan Chen1Wantong Zhao2Junhao Zheng3Yanhong Zhang4Aixiang Lv5Jingmin Li6Hua Cao7Liangpu Xu8Hailong Huang9Medical 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 DefectMedical 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 DefectMedical 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 DefectMedical 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 DefectMedical 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 DefectMedical 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 DefectMedical 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 DefectMedical 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 DefectMedical 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 DefectMedical 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 DefectAbstract 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.https://doi.org/10.1186/s13023-025-03806-0β-thalassemiamiR-17-3pBCL11AHbFErythropoiesis |
| spellingShingle | Siwen Zhang Meihuan Chen Wantong Zhao Junhao Zheng Yanhong Zhang Aixiang Lv Jingmin Li Hua Cao Liangpu Xu Hailong Huang Upregulation of miR-17-3p is associated with HbF in patients with β-thalassemia and induces γ-globin expression by targeting BCL11A Orphanet Journal of Rare Diseases β-thalassemia miR-17-3p BCL11A HbF Erythropoiesis |
| title | Upregulation of miR-17-3p is associated with HbF in patients with β-thalassemia and induces γ-globin expression by targeting BCL11A |
| title_full | Upregulation of miR-17-3p is associated with HbF in patients with β-thalassemia and induces γ-globin expression by targeting BCL11A |
| title_fullStr | Upregulation of miR-17-3p is associated with HbF in patients with β-thalassemia and induces γ-globin expression by targeting BCL11A |
| title_full_unstemmed | Upregulation of miR-17-3p is associated with HbF in patients with β-thalassemia and induces γ-globin expression by targeting BCL11A |
| title_short | Upregulation of miR-17-3p is associated with HbF in patients with β-thalassemia and induces γ-globin expression by targeting BCL11A |
| title_sort | upregulation of mir 17 3p is associated with hbf in patients with β thalassemia and induces γ globin expression by targeting bcl11a |
| topic | β-thalassemia miR-17-3p BCL11A HbF Erythropoiesis |
| url | https://doi.org/10.1186/s13023-025-03806-0 |
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