Effect of hydroxyurea on SP1, LIN28B, IGF2BP3, COL4A5, BCL2, gamma globin genes expression: an in vitro study

Background In some [beta]-thalassemia intermedia patients, hydroxyurea (HU) increases hemoglobin and HbF levels. However, HUs' effects molecular mechanism is still unclear. Methods In this study, a weighted gene co-expression network analysis was conducted on the GSE109186 dataset. The genes LI...

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Bibliographic Details
Published in:Egyptian Journal of Medical Human Genetics 2023-12, Vol.24 (1), p.72-8
Main Authors: Fashami, Akram Agha-Amini, Alemzadeh, Esmat, Safarpour, Hossein, Miri-Moghaddam, Ebrahim
Format: Article
Language:English
Subjects:
Analysis
Bcl-2 protein
Blood diseases
Blood transfusions
Bone marrow
Datasets
Gene expression
Genes
Glycosylated hemoglobin
Hemoglobin
Hemoglobin F
Hydroxyurea
Kinases
Statistical analysis
Thalassemia
Thermal cycling
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Summary:Background In some [beta]-thalassemia intermedia patients, hydroxyurea (HU) increases hemoglobin and HbF levels. However, HUs' effects molecular mechanism is still unclear. Methods In this study, a weighted gene co-expression network analysis was conducted on the GSE109186 dataset. The genes LIN28A, COL4A5, SP1, BCL2, and IGF2BP3 were identified as hub genes involved in the [gamma]-gene switching process. The effect of HU treatment at doses of 50, 100, and 150 [mu]M for 12, 24, and 48 h on the K562 cell line was examined by using qRT-PCR to measure the expression levels of these hub genes. Results SP1 gene expression decreased after treatment with 50, 100, and 150 [mu]M HU for 12, 24, and 48 h. The expression of the LIN28A gene was tripled at three concentrations of 50, 100, and 150 [mu]M for 12 h. The IGF2BP3 gene expression was doubled after 24 and 48 h at a concentration of 150 [mu]M HU. Regarding COL4A5 gene expression, except at 12 h after treatment at a concentration of 50 [mu]M, a significant increase was observed in other concentrations and times. The BCL2 gene expression pattern at all concentrations decreased significantly after 12 h. The [gamma] gene showed a significant increase compared to the control group after 24 and 48 h at the different concentrations. Conclusion The results showed that in HU-treated cells, changes in the expression of LIN28A, COL4A5, SP1, and IGF2BP3 genes were accompanied by an increase in [gamma]-gene expression. By elucidating precisely the mechanism of [gamma]-to-[beta] gene switching, we can hope for less complicated drugs.
ISSN:1110-8630
2090-2441
DOI:10.1186/s43042-023-00452-8