Journal
BLOOD CELLS MOLECULES AND DISEASES
Volume 87, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bcmd.2020.102523
Keywords
HbE/beta-thalassemia; Fetal hemoglobin; MicroRNA array; Pathway; MicroRNA cluster
Categories
Funding
- Sponsored Research & Industrial Consultancy (SRIC), Indian Institute of Technology Kharagpur [IIT/SRIC/SMST/BHA/2015-16/122]
- Council of Scientific and Industrial Research (CSIR), India [IIT/SRIC/SMST/BHA/2015-16/122, 09/081(1267)/2015-EMR-I]
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This study investigated the miRNA expression profile of hematopoietic progenitor cells in HbE/beta-thalassemia patients and identified key miRNAs that may be involved in regulating HbF levels. The dysregulated miRNAs were found to be associated with biological processes and molecular functions such as MAPK and HIF-1 signaling pathways. The results suggest that manipulation of these key miRNAs could potentially elevate HbF levels in beta-hemoglobinopathies.
Hemoglobin E (HbE)/beta-thalassemia is a form of beta-hemoglobinopathy that is well-known for its clinical heterogeneity. Individuals suffering from this condition are often found to exhibit increased fetal hemoglobin (HbF) levels - a factor that may contribute to their reduced blood transfusion requirements. This study hypothesized that the high HbF levels in HbE/beta-thalassemia individuals may be guided by microRNAs and explored their involvement in the disease pathophysiology. The miRNA expression profile of hematopoietic progenitor cells in HbE/beta-thalassemia patients was investigated and compared with that of healthy controls. Using miRNA PCR array experiments, eight miRNAs (hsa-miR-146a-5p, hsa-miR-146b-5p, hsa-miR-148b-3p, hsa-miR-155-5p, hsamiR-192-5p, hsa-miR-335-5p, hsa-miR-7-5p, hsa-miR-98-5p) were identified to be significantly up-regulated whereas four miRNAs (hsa-let-7a-5p, hsa-miR-320a, hsa-let-7b-5p, hsa-miR-92a-3p) were significantly down regulated. Target analysis found them to be associated with several biological processes and molecular functions including MAPK and HIF-1 signaling pathways - the pathways known to be associated with HbF upregulation. Results of dysregulated miRNAs further indicated that miR-17/92 cluster might be of critical importance in HbF regulation. The findings of our study thus identify key miRNAs that can be extrinsically manipulated to elevate HbF levels in beta-hemoglobinopathies.
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