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

• 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: sickle cell disease; fetal hemoglobin; hydroxyurea; miRNA; Africa
• Online Access: https://www.frontiersin.org/article/10.3389/fgene.2019.00509/full
• ISSN: 1664-8021

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.