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Article Open Access

Upregulation of miR‑6747‑3p affects red blood cell lineage development and induces fetal hemoglobin expression by targeting BCL11A in β‑thalassemia

  • Authors:
    • Aixiang Lv
    • Meihuan Chen
    • Siwen Zhang
    • Wantong Zhao
    • Jingmin Li
    • Siyang Lin
    • Yanping Zheng
    • Na Lin
    • Liangpu Xu
    • Hailong Huang
  • View Affiliations / Copyright

    Affiliations: College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian 350004, P.R. China, Medical Genetic Diagnosis and Therapy Center of Fujian Maternity and Child Health Hospital, Fujian Provincial Key Laboratory of Prenatal Diagnosis and Birth Defects, Fuzhou, Fujian 350001, P.R. China
    Copyright: © Lv et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 7
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    Published online on: October 18, 2024
       https://doi.org/10.3892/mmr.2024.13372
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Abstract

In β‑thalassemia, excessive α‑globin chain impedes the normal development of red blood cells resulting in anemia. Numerous miRNAs, including miR‑6747‑3p, are aberrantly expressed in β‑thalassemia major (β‑TM), but there are no reports on the mechanism of miR‑6747‑3p in regulating red blood cell lineage development and fetal hemoglobin (HbF) expression. In the present study, RT‑qPCR was utilized to confirm miR‑6747‑3p expression in patients with β‑TM and the healthy controls. Electrotransfection was employed to introduce the miR‑6747‑3p mimic and inhibitor in both HUDEP‑2 and K562 cells, and red blood cell lineage development was evaluated by CCK‑8 assay, flow cytometry, Wright‑Giemsa staining and Benzidine blue staining. B‑cell lymphoma/leukemia 11A (BCL11A) was selected as a candidate target gene of miR‑6747‑3p for further validation through FISH assay, dual luciferase assay and Western blotting. The results indicated that miR‑6747‑3p expression was notably higher in patients with β‑TM compared with healthy controls and was positively related to HbF levels. Functionally, miR‑6747‑3p overexpression resulted in the hindrance of cell proliferation, promotion of cell apoptosis, facilitation of cellular erythroid differentiation and γ‑globin expression in HUDEP‑2 and K562 cells. Mechanistically, miR‑6747‑3p could specifically bind to the 546‑552 loci of BCL11A 3'‑UTR and induce γ‑globin expression. These data indicate that upregulation of miR‑6747‑3p affects red blood cell lineage development and induces HbF expression by targeting BCL11A in β‑thalassemia, highlighting miR‑6747‑3p as a potential molecular target for β‑thalassemia therapy.
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Copy and paste a formatted citation
Spandidos Publications style
Lv A, Chen M, Zhang S, Zhao W, Li J, Lin S, Zheng Y, Lin N, Xu L, Huang H, Huang H, et al: Upregulation of miR‑6747‑3p affects red blood cell lineage development and induces fetal hemoglobin expression by targeting BCL11A in β‑thalassemia. Mol Med Rep 31: 7, 2025.
APA
Lv, A., Chen, M., Zhang, S., Zhao, W., Li, J., Lin, S. ... Huang, H. (2025). Upregulation of miR‑6747‑3p affects red blood cell lineage development and induces fetal hemoglobin expression by targeting BCL11A in β‑thalassemia. Molecular Medicine Reports, 31, 7. https://doi.org/10.3892/mmr.2024.13372
MLA
Lv, A., Chen, M., Zhang, S., Zhao, W., Li, J., Lin, S., Zheng, Y., Lin, N., Xu, L., Huang, H."Upregulation of miR‑6747‑3p affects red blood cell lineage development and induces fetal hemoglobin expression by targeting BCL11A in β‑thalassemia". Molecular Medicine Reports 31.1 (2025): 7.
Chicago
Lv, A., Chen, M., Zhang, S., Zhao, W., Li, J., Lin, S., Zheng, Y., Lin, N., Xu, L., Huang, H."Upregulation of miR‑6747‑3p affects red blood cell lineage development and induces fetal hemoglobin expression by targeting BCL11A in β‑thalassemia". Molecular Medicine Reports 31, no. 1 (2025): 7. https://doi.org/10.3892/mmr.2024.13372
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Spandidos Publications style
Lv A, Chen M, Zhang S, Zhao W, Li J, Lin S, Zheng Y, Lin N, Xu L, Huang H, Huang H, et al: Upregulation of miR‑6747‑3p affects red blood cell lineage development and induces fetal hemoglobin expression by targeting BCL11A in β‑thalassemia. Mol Med Rep 31: 7, 2025.
APA
Lv, A., Chen, M., Zhang, S., Zhao, W., Li, J., Lin, S. ... Huang, H. (2025). Upregulation of miR‑6747‑3p affects red blood cell lineage development and induces fetal hemoglobin expression by targeting BCL11A in β‑thalassemia. Molecular Medicine Reports, 31, 7. https://doi.org/10.3892/mmr.2024.13372
MLA
Lv, A., Chen, M., Zhang, S., Zhao, W., Li, J., Lin, S., Zheng, Y., Lin, N., Xu, L., Huang, H."Upregulation of miR‑6747‑3p affects red blood cell lineage development and induces fetal hemoglobin expression by targeting BCL11A in β‑thalassemia". Molecular Medicine Reports 31.1 (2025): 7.
Chicago
Lv, A., Chen, M., Zhang, S., Zhao, W., Li, J., Lin, S., Zheng, Y., Lin, N., Xu, L., Huang, H."Upregulation of miR‑6747‑3p affects red blood cell lineage development and induces fetal hemoglobin expression by targeting BCL11A in β‑thalassemia". Molecular Medicine Reports 31, no. 1 (2025): 7. https://doi.org/10.3892/mmr.2024.13372
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