Hydroxyurea-Induced miRNA Expression in Sickle Cell Disease Patients in Africa

Hydroxyurea (HU) is clinically beneficial in sickle cell disease (SCD) through fetal hemoglobin (HbF) induction; however, the mechanism of HU is not yet fully elucidated. Selected miRNAs have been associated with HU-induced HbF production. We have investigated differential HU-induced global miRNA ex...

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Main Authors: Khuthala Mnika, Gaston K. Mazandu, Mario Jonas, Gift D. Pule, Emile R. Chimusa, Neil A. Hanchard, Ambroise Wonkam
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-05-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fgene.2019.00509/full
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author Khuthala Mnika
Gaston K. Mazandu
Gaston K. Mazandu
Mario Jonas
Gift D. Pule
Emile R. Chimusa
Neil A. Hanchard
Ambroise Wonkam
author_facet Khuthala Mnika
Gaston K. Mazandu
Gaston K. Mazandu
Mario Jonas
Gift D. Pule
Emile R. Chimusa
Neil A. Hanchard
Ambroise Wonkam
author_sort Khuthala Mnika
collection DOAJ
description Hydroxyurea (HU) is clinically beneficial in sickle cell disease (SCD) through fetal hemoglobin (HbF) induction; however, the mechanism of HU is not yet fully elucidated. Selected miRNAs have been associated with HU-induced HbF production. We have investigated differential HU-induced global miRNA expression in peripheral blood of adult SCD patients in patients from Congo, living in South Africa. We found 22 of 798 miRNAs evaluated that were differentially expressed under HU treatment, with the majority (13/22) being functionally associated with HbF-regulatory genes, including BCL11A (miR-148b-3p, miR-32-5p, miR-340-5p, and miR-29c-3p), MYB (miR-105-5p), and KLF-3 (miR-106b-5), and SP1 (miR-29b-3p, miR-625-5p, miR-324-5p, miR-125a-5p, miR-99b-5p, miR-374b-5p, and miR-145-5p). The preliminary study provides potential additional miRNA candidates for therapeutic exploration.
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spelling doaj.art-f5661fb2d8f74c3b924a34b60cad6ba12022-12-22T02:01:49ZengFrontiers Media S.A.Frontiers in Genetics1664-80212019-05-011010.3389/fgene.2019.00509437181Hydroxyurea-Induced miRNA Expression in Sickle Cell Disease Patients in AfricaKhuthala Mnika0Gaston K. Mazandu1Gaston K. Mazandu2Mario Jonas3Gift D. Pule4Emile R. Chimusa5Neil A. Hanchard6Ambroise Wonkam7Division of Human Genetics, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South AfricaDivision of Human Genetics, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South AfricaAfrican Institute for Mathematical Sciences, Cape Town, South AfricaDivision of Human Genetics, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South AfricaDivision of Human Genetics, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South AfricaDivision of Human Genetics, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South AfricaDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United StatesDivision of Human Genetics, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South AfricaHydroxyurea (HU) is clinically beneficial in sickle cell disease (SCD) through fetal hemoglobin (HbF) induction; however, the mechanism of HU is not yet fully elucidated. Selected miRNAs have been associated with HU-induced HbF production. We have investigated differential HU-induced global miRNA expression in peripheral blood of adult SCD patients in patients from Congo, living in South Africa. We found 22 of 798 miRNAs evaluated that were differentially expressed under HU treatment, with the majority (13/22) being functionally associated with HbF-regulatory genes, including BCL11A (miR-148b-3p, miR-32-5p, miR-340-5p, and miR-29c-3p), MYB (miR-105-5p), and KLF-3 (miR-106b-5), and SP1 (miR-29b-3p, miR-625-5p, miR-324-5p, miR-125a-5p, miR-99b-5p, miR-374b-5p, and miR-145-5p). The preliminary study provides potential additional miRNA candidates for therapeutic exploration.https://www.frontiersin.org/article/10.3389/fgene.2019.00509/fullsickle cell diseasefetal hemoglobinhydroxyureamiRNAAfrica
spellingShingle Khuthala Mnika
Gaston K. Mazandu
Gaston K. Mazandu
Mario Jonas
Gift D. Pule
Emile R. Chimusa
Neil A. Hanchard
Ambroise Wonkam
Hydroxyurea-Induced miRNA Expression in Sickle Cell Disease Patients in Africa
Frontiers in Genetics
sickle cell disease
fetal hemoglobin
hydroxyurea
miRNA
Africa
title Hydroxyurea-Induced miRNA Expression in Sickle Cell Disease Patients in Africa
title_full Hydroxyurea-Induced miRNA Expression in Sickle Cell Disease Patients in Africa
title_fullStr Hydroxyurea-Induced miRNA Expression in Sickle Cell Disease Patients in Africa
title_full_unstemmed Hydroxyurea-Induced miRNA Expression in Sickle Cell Disease Patients in Africa
title_short Hydroxyurea-Induced miRNA Expression in Sickle Cell Disease Patients in Africa
title_sort hydroxyurea induced mirna expression in sickle cell disease patients in africa
topic sickle cell disease
fetal hemoglobin
hydroxyurea
miRNA
Africa
url https://www.frontiersin.org/article/10.3389/fgene.2019.00509/full
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