Epigenetic effects toward new insights as potential therapeutic target in B-thalassemia
Abstract Background Fetal hemoglobin (HbF) induction has shown promise for the treatment of β-hemoglobinopathies. HbF induction in β-thalassemia could overcome ineffective hematopoiesis and thus terminate transfusion dependency for formerly transfusion dependant patients. Several miRNAs have been fo...
| Principais autores: | , , , , |
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| Formato: | Artigo |
| Idioma: | English |
| Publicado em: |
Elsevier
2021-03-01
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| coleção: | Journal of Genetic Engineering and Biotechnology |
| Assuntos: | |
| Acesso em linha: | https://doi.org/10.1186/s43141-021-00138-x |
| _version_ | 1827279230561419264 |
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| author | Noha Hamdy Eltaweel Ghada Youssef ElKamah Rabab Khairat Hanan Abd Elmawgoud Atia Khalda S. Amr |
| author_facet | Noha Hamdy Eltaweel Ghada Youssef ElKamah Rabab Khairat Hanan Abd Elmawgoud Atia Khalda S. Amr |
| author_sort | Noha Hamdy Eltaweel |
| collection | DOAJ |
| description | Abstract Background Fetal hemoglobin (HbF) induction has shown promise for the treatment of β-hemoglobinopathies. HbF induction in β-thalassemia could overcome ineffective hematopoiesis and thus terminate transfusion dependency for formerly transfusion dependant patients. Several miRNAs have been found to reactivate γ-globin expression and increase HbF. In this study, we aimed to investigate the expression of 4 miRNAs (miR-15a, miR-16-1, miR-96, and miR-486-3p) in high HbF thalassemia patients and correlate their levels with the patients’ HbF levels then, in order to predict the exact role of the studied miRNAs in hematopoiesis, a bioinformatic analysis was carried out. We went through this bioinformatic analysis to determine the network of genes regulated by miRNAs and further investigate the interaction between all of them through their involvement in hematopoiesis. In this study, the differential expression was measured by qRT-PCR for 40 patients with high HbF and compared to 20 healthy controls. Bioinformatics was conducted involving functional annotation and pathway enrichment analyses. Results The studied microRNAs were significantly deregulated in thalassemia patients in correlation with HbF. Functional annotation and pathway enrichment analyses revealed a major role of miR-486-3p and miR-15a in HbF induction. Conclusion MiR-486-3p and miR-15a are crucial for HbF induction. Further validating studies are needed. |
| first_indexed | 2024-04-24T08:15:37Z |
| format | Article |
| id | doaj.art-00819864096e44f385d25859494fe326 |
| institution | Directory Open Access Journal |
| issn | 2090-5920 |
| language | English |
| last_indexed | 2024-04-24T08:15:37Z |
| publishDate | 2021-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Genetic Engineering and Biotechnology |
| spelling | doaj.art-00819864096e44f385d25859494fe3262024-04-17T03:46:50ZengElsevierJournal of Genetic Engineering and Biotechnology2090-59202021-03-0119111210.1186/s43141-021-00138-xEpigenetic effects toward new insights as potential therapeutic target in B-thalassemiaNoha Hamdy Eltaweel0Ghada Youssef ElKamah1Rabab Khairat2Hanan Abd Elmawgoud Atia3Khalda S. Amr4Medical Molecular Genetics Department, Human genetics and genome project Division, National Research CentreClinical Genetics Department, Human genetics and genome project Division, National Research CentreMedical Molecular Genetics Department, Human genetics and genome project Division, National Research CentrePharmacology and Toxicology Department, College of Pharmacy, Hail UniversityMedical Molecular Genetics Department, Human genetics and genome project Division, National Research CentreAbstract Background Fetal hemoglobin (HbF) induction has shown promise for the treatment of β-hemoglobinopathies. HbF induction in β-thalassemia could overcome ineffective hematopoiesis and thus terminate transfusion dependency for formerly transfusion dependant patients. Several miRNAs have been found to reactivate γ-globin expression and increase HbF. In this study, we aimed to investigate the expression of 4 miRNAs (miR-15a, miR-16-1, miR-96, and miR-486-3p) in high HbF thalassemia patients and correlate their levels with the patients’ HbF levels then, in order to predict the exact role of the studied miRNAs in hematopoiesis, a bioinformatic analysis was carried out. We went through this bioinformatic analysis to determine the network of genes regulated by miRNAs and further investigate the interaction between all of them through their involvement in hematopoiesis. In this study, the differential expression was measured by qRT-PCR for 40 patients with high HbF and compared to 20 healthy controls. Bioinformatics was conducted involving functional annotation and pathway enrichment analyses. Results The studied microRNAs were significantly deregulated in thalassemia patients in correlation with HbF. Functional annotation and pathway enrichment analyses revealed a major role of miR-486-3p and miR-15a in HbF induction. Conclusion MiR-486-3p and miR-15a are crucial for HbF induction. Further validating studies are needed.https://doi.org/10.1186/s43141-021-00138-xThalassemia therapyHbF inductionMicroRNAmiR-15amiR-16-1miR-96 |
| spellingShingle | Noha Hamdy Eltaweel Ghada Youssef ElKamah Rabab Khairat Hanan Abd Elmawgoud Atia Khalda S. Amr Epigenetic effects toward new insights as potential therapeutic target in B-thalassemia Journal of Genetic Engineering and Biotechnology Thalassemia therapy HbF induction MicroRNA miR-15a miR-16-1 miR-96 |
| title | Epigenetic effects toward new insights as potential therapeutic target in B-thalassemia |
| title_full | Epigenetic effects toward new insights as potential therapeutic target in B-thalassemia |
| title_fullStr | Epigenetic effects toward new insights as potential therapeutic target in B-thalassemia |
| title_full_unstemmed | Epigenetic effects toward new insights as potential therapeutic target in B-thalassemia |
| title_short | Epigenetic effects toward new insights as potential therapeutic target in B-thalassemia |
| title_sort | epigenetic effects toward new insights as potential therapeutic target in b thalassemia |
| topic | Thalassemia therapy HbF induction MicroRNA miR-15a miR-16-1 miR-96 |
| url | https://doi.org/10.1186/s43141-021-00138-x |
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