In some β-thalassemia intermedia patients, hydroxyurea (HU) increases hemoglobin and HbF levels. However, HUs’ effects molecular mechanism is still unclear. 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 γ-gene switching process. The effect of HU treatment at doses of 50, 100, and 150 μM 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. SP1 gene expression decreased after treatment with 50, 100, and 150 μM HU for 12, 24, and 48 h. The expression of the LIN28A gene was tripled at three concentrations of 50, 100, and 150 μM for 12 h. The IGF2BP3 gene expression was doubled after 24 and 48 h at a concentration of 150 μM HU. Regarding COL4A5 gene expression, except at 12 h after treatment at a concentration of 50 μM, a significant increase was observed in other concentrations and times. The BCL2 gene expression pattern at all concentrations decreased significantly after 12 h. The γ gene showed a significant increase compared to the control group after 24 and 48 h at the different concentrations. 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 γ-gene expression. By elucidating precisely the mechanism of γ-to-β gene switching, we can hope for less complicated drugs.

中文翻译：

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羟基脲对 SP1、LIN28B、IGF2BP3、COL4A5、BCL2、γ 球蛋白基因表达的影响：一项体外研究

在一些中间型 β 地中海贫血患者中，羟基脲 (HU) 会增加血红蛋白和 HbF 水平。然而，HUs的作用分子机制仍不清楚。在本研究中，对 GSE109186 数据集进行了加权基因共表达网络分析。基因 LIN28A、COL4A5、SP1、BCL2 和 IGF2BP3 被确定为参与 γ 基因转换过程的枢纽基因。通过使用 qRT-PCR 测量这些 hub 基因的表达水平，检查了 50、100 和 150 μM 剂量的 HU 处理 12、24 和 48 小时对 K562 细胞系的影响。用 50、100 和 150 μM HU 处理 12、24 和 48 小时后，SP1 基因表达下降。在 50、100 和 150 μM 三个浓度下 12 小时，LIN28A 基因的表达增加了三倍。在 150 μM HU 浓度下 24 小时和 48 小时后，IGF2BP3 基因表达加倍。关于COL4A5基因表达，除了50μM浓度处理后12小时外，其他浓度和时间均观察到显着增加。12小时后，所有浓度的BCL2基因表达模式均显着下降。不同浓度24小时和48小时后，γ基因较对照组显着增加。结果显示，在HU处理的细胞中，LIN28A、COL4A5、SP1和IGF2BP3基因表达的变化伴随着γ基因表达的增加。通过精确阐明 γ 到 β 基因转换的机制，我们有望开发出不太复杂的药物。