Upregulation of miR-214 Mediates Oxidative Stress in Hb H Disease <i>via</i> Targeting of <i>ATF4</i>

Saensuwanna, Apisara; Penglong, Tipparat; Srinoun, Kanitta

doi:10.1080/03630269.2021.1941081

Cited by 4 publications

(7 citation statements)

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“…Several studies have shown that miRNAs are involved in regulating oxidative stress in many cell types, including RBCs. In this study, we focused on miR-214, which has previously been shown to play a role in oxidative stress in erythroid cells [ 13 , 25 ]. Our previous study revealed upregulation of miR-214 and downregulation of ATF4 mRNA target in the reticulocytes of patients with HbH disease.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous study revealed upregulation of miR-214 and downregulation of ATF4 mRNA target in the reticulocytes of patients with HbH disease. Moreover, we found an association between miR-214 expression, oxidative stress condition, and the severity of anemia [ 13 ]. Here, we revealed that the expression of miR-214 is increased in a dose-dependent manner by the oxidative stress inducer hemin.…”

Section: Discussionmentioning

confidence: 99%

“…However, the effect of miR-214 may differ in late-stage erythroid cells. Our previous study showed a significant difference in the role of miR-214 in oxidative stress regulation between HbH disease and β-thalassemia/HbE in reticulocytes, which appears in the late stage of erythroid cells [ 13 ]. The significantly higher expression of miR-214 in reticulocytes was associated with the higher ROS levels in HbH disease when compared to β-thalassemia/HbE.…”

Section: Discussionmentioning

confidence: 99%

“…High ATF4 expression was observed when a heme-regulated inhibitor of protein translation (HRI) phosphorylated eukaryotic translation initiation factor 2alpha (eIF2alpha) to diminish oxidative stress in erythrocytes [ 14 , 16 ]. ATF4 is a mRNA target of miR-214 [ 13 , 25 ]. In our study, downregulation of ATF4 mRNA level was observed in both the thalassemia groups—this implied that miR-214 might lead to downregulation of ATF4, which could further promote oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the expression level of miR-214 was positively associated with ROS levels. A reduction in the mRNA of activating transcription factor 4 (ATF4) was observed in both, HbH (β4) disease, and β-thalassemia/Hb E thalassemia groups [ 13 ]. ATF4 is a crucial transcription factor that responds to cellular stress.…”

Section: Introductionmentioning

confidence: 99%

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miR-214 aggravates oxidative stress in thalassemic erythroid cells by targeting ATF4

Penglong,

Saensuwanna,

Jantapaso

et al. 2024

PLoS ONE

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

miR-214 aggravates oxidative stress in thalassemic erythroid cells by targeting ATF4

Penglong,

Saensuwanna,

Jantapaso

et al. 2024

PLoS ONE

Self Cite

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Novel insights into the activating transcription factor 4 in Alzheimer’s disease and associated aging-related diseases: Mechanisms and therapeutic implications

Zhang,

Nao,

Zhang

et al. 2024

Frontiers in Neuroendocrinology

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Post-transcriptional regulation of erythropoiesis

Zhang

et al. 2023

Blood Science

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Erythropoiesis is a complex, precise, and lifelong process that is essential for maintaining normal body functions. Its strict regulation is necessary to prevent a variety of blood diseases. Normal erythropoiesis is precisely regulated by an intricate network that involves transcription levels, signal transduction, and various epigenetic modifications. In recent years, research on post-transcriptional levels in erythropoiesis has expanded significantly. The dynamic regulation of splicing transitions is responsible for changes in protein isoform expression that add new functions beneficial for erythropoiesis. RNA-binding proteins adapt the translation of transcripts to the protein requirements of the cell, yielding mRNA with dynamic translation efficiency. Noncoding RNAs, such as microRNAs and lncRNAs, are indispensable for changing the translational efficiency and/or stability of targeted mRNAs to maintain the normal expression of genes related to erythropoiesis. N6-methyladenosine-dependent regulation of mRNA translation plays an important role in maintaining the expression programs of erythroid-related genes and promoting erythroid lineage determination. This review aims to describe our current understanding of the role of post-transcriptional regulation in erythropoiesis and erythroid-associated diseases, and to shed light on the physiological and pathological implications of the post-transcriptional regulation machinery in erythropoiesis. These may help to further enrich our understanding of the regulatory network of erythropoiesis and provide new strategies for the diagnosis and treatment of erythroid-related diseases.

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Upregulation of miR-214 Mediates Oxidative Stress in Hb H Disease via Targeting of ATF4

Cited by 4 publications

References 30 publications

miR-214 aggravates oxidative stress in thalassemic erythroid cells by targeting ATF4

miR-214 aggravates oxidative stress in thalassemic erythroid cells by targeting ATF4

Novel insights into the activating transcription factor 4 in Alzheimer’s disease and associated aging-related diseases: Mechanisms and therapeutic implications

Post-transcriptional regulation of erythropoiesis

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