Department of Pathology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand.
Faculty of Medical Technology, Prince of Songkla University, Hat Yai, Songkhla, Thailand.
PLoS One. 2024 Apr 16;19(4):e0300958. doi: 10.1371/journal.pone.0300958. eCollection 2024.
Oxidative damage to erythroid cells plays a key role in the pathogenesis of thalassemia. The oxidative stress in thalassemia is potentiated by heme, nonheme iron, and free iron produced by the Fenton reaction, due to degradation of the unstable hemoglobin and iron overload. In addition, the levels of antioxidant enzymes and molecules are significantly decreased in erythrocytes in α- and β-thalassemia. The control of oxidative stress in red blood cells (RBCs) is known to be mediated by microRNAs (miRNAs). In erythroid cells, microR-214 (miR-214) has been reported to respond to external oxidative stress. However, the molecular mechanisms underlying this phenomenon remain unclear, especially during thalassemic erythropoiesis. In the present study, to further understand how miR-214 aggravates oxidative stress in thalassemia erythroid cells, we investigated the molecular mechanism of miR-214 and its regulation of the oxidative status in thalassemia erythrocytes. We have reported a biphasic expression of miR-214 in β- and α-thalassemia. In the present study the effect of miR-214 expression was investigated by using miR -inhibitor and -mimic transfection in erythroid cell lines induced by hemin. Our study showed a biphasic expression of miR-214 in β- and α-thalassemia. Subsequently, we examined the effect of miR-214 on erythroid differentiation in thalassemia. Our study reveals the loss-of-function of miR-214 during translational activation of activating transcription factor 4 mRNA, leading to decreased reactive oxygen species levels and increased glutathione levels in thalassemia erythroid cell. Our results suggest that the expression of activating transcription factor 4 regulated by miR-214 is important for oxidative stress modulation in thalassemic erythroid cells. Our findings can help to better understand the molecular mechanism of miRNA and transcription factors in regulation of oxidative status in erythroid cells, particularly in thalassemia, and could be useful for managing and relieving severe anemia symptoms in patients in the future.
红细胞的氧化损伤在珠蛋白生成障碍性贫血的发病机制中起关键作用。由于不稳定血红蛋白的降解和铁过载，铁卟啉、非铁卟啉铁和 Fenton 反应产生的游离铁会加剧珠蛋白生成障碍性贫血中的氧化应激。此外，α-和β-珠蛋白生成障碍性贫血患者的红细胞中抗氧化酶和分子的水平显著降低。已知红细胞（RBC）中的氧化应激受 microRNAs（miRNAs）控制。在红细胞中，microR-214（miR-214）已被报道对外界氧化应激有反应。然而，这种现象的分子机制尚不清楚，特别是在珠蛋白生成障碍性贫血的红细胞生成过程中。在本研究中，为了进一步了解 miR-214 如何加剧珠蛋白生成障碍性贫血红细胞的氧化应激，我们研究了 miR-214 的分子机制及其对珠蛋白生成障碍性贫血红细胞氧化状态的调节。我们已经报道了 miR-214 在β-和α-珠蛋白生成障碍性贫血中的双相表达。在本研究中，我们通过用 miR-抑制剂和 mimic 转染血红素诱导的红细胞系来研究 miR-214 的表达效果。我们的研究表明，miR-214 在β-和α-珠蛋白生成障碍性贫血中呈双相表达。随后，我们研究了 miR-214 对珠蛋白生成障碍性贫血中红细胞分化的影响。我们的研究揭示了 miR-214 在翻译激活激活转录因子 4 mRNA 时的功能丧失，导致珠蛋白生成障碍性贫血红细胞中活性氧水平降低和谷胱甘肽水平升高。我们的结果表明，miR-214 调节的激活转录因子 4 的表达对于珠蛋白生成障碍性贫血红细胞的氧化应激调节很重要。我们的发现可以帮助更好地理解 miRNA 和转录因子在红细胞氧化状态调节中的分子机制，特别是在珠蛋白生成障碍性贫血中，这对未来管理和缓解患者严重贫血症状可能有用。
