Circulating miRNAs and tissue iron overload in transfusion-dependent β-thalassemia major: novel predictors and follow-up guide

El-Khazragy⃰, Nashwa; Matbouly, Safa; Hanna, Demiana H.; Mahran, Nievin Ahmed; Mostafa, Sally Abdallah; Abdelrehim, Bassam A.; Farouk, Yasmeen K; Abuelela, Soha

doi:10.1007/s00277-021-04639-0

Cited by 3 publications

(4 citation statements)

References 46 publications

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“…Kuno et al demonstrated that elevated miR-125b expression from activated phagocytic monocytes was a genetic modifier related to anemia severity in β-thal patients [21]. El-Khazragy et al suggested that plasma-dysregulated miR-let-7d, miR-122, and miR-200 served as novel and non-invasive predictor biomarkers for cellular damage under condition of tissue iron excess in transfusion-dependent β-thal patients [22]. Recently, a cross-sectional study concluded that circulating MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) and MIAT (myocardial infarction-associated transcript) were promising predictors for blood transfusion status in β-thal patients [23].…”

Section: Discussionmentioning

confidence: 99%

Peripheral blood circular RNA circ-0008102 may serve as a novel clinical biomarker in beta-thalassemia patients

Chen,

Lv,

Zhang

et al. 2024

Eur J Pediatr

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Circular RNA circ-0008102 has previously been found dysregulated in β-thalassemia (β-thal) in circRNAs microarray (GSE196682 and GSE241141). Our study is aimed at identifying whether circ-0008102 could be a novel biomarker in β-thal. The peripheral blood of pediatric β-thal patients with (n = 39) or without (n = 20) blood transfusion and healthy controls (n = 30) was selected. qRT-PCR, ROC curve analysis, Spearman correlation analysis, and FISH were used to analyze clinical value of circ-0008102. qRT-PCR confirmed that circ-0008102 expression in pediatric β-thal patients without blood transfusion was significantly higher. ROC curves analysis showed that the AUC of circ-0008102 for differentiating patients without blood transfusion from patients with blood transfusion and healthy controls with an AUC of 0.733 and 0.711. Furthermore, circ-0008102 expression was positively correlated with the levels of RBC, HbF, β-globin, and γ-globin mRNA, but was negatively corrected with the levels of HbA and Cr. circ-0008102 was mainly located in the cytoplasm. circ-0008102 could induce the activation of γ-globin and negatively regulate the expression of the five highest-ranking candidate miRNAs (miR-372-3p, miR-329-5p, miR-198, miR-152-5p, and miR-627-3p) in K562 cells.Conclusion: We demonstrate that peripheral blood upregulated circ-0008102 may serve as a novel clinical biomarker for pediatric β-thal without blood transfusion. What is known:• CircRNAs are known to be involved in various human diseases, and several circRNAs are regarded as a class of promising blood-based biomarkers for detection of β-thal.• CircRNAs exert biological functions by epigenetic modification and gene expression regulation, and dysregulated circRNAs in β-thal might be involved in the induction of HbF in β-thal. What is new:• Peripheral blood circ-0008102 maybe serve as a novel clinical biomarker for detection of pediatric β-thal without blood transfusion.• Circ-0008102 participates in the pathogenesis of β-thal through regulating γ-globin expression, and negatively regulates the expression of miR-372-3p, miR-329-5p, miR-198, miR-152-5p and miR-627-3p.

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Section: Discussionmentioning

confidence: 99%

Peripheral blood circular RNA circ-0008102 may serve as a novel clinical biomarker in beta-thalassemia patients

Chen,

Lv,

Zhang

et al. 2024

Eur J Pediatr

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“…Recently, miRNAs have been implicated as critical oxidative stress and iron overload regulators 22 . MiRNAs are essential molecules that regulate critical enzymes in ROS synthesis/inhibition and have received much attention from researchers in ischemia/reperfusion injury, tumors, and iron overload diseases 9,23,24 . Elevated serum levels of miR-34a and miR-122 were associated with decreased activities of antioxidant enzymes in ischemia/reperfusion injury of the rat liver 25 .…”

Section: Discussionmentioning

confidence: 99%

“…MicroRNA (miRNA) is a class of small noncoding single-stranded RNAs, usually consisting of 21 to 25 nucleotides. miRNAs are critical regulators of pathologic processes, such as immune response 8 , macrophage polarization 8 , iron overload 9 , oxidative stress 10 , and chronic inflammation 11 . Due to their stability and low immunogenicity, miRNAs have been used as biomarkers for the noninvasive clinical diagnosis of various diseases 12 .…”

Section: Introductionmentioning

confidence: 99%

Analysis of microRNA expression profiles involved oxidative stress in a deep tissue pressure injury

Wang,

Shan,

Zhang

2023

Interdisciplinary Nursing Research

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Objective: To investigate the association between oxidative stress and the development of deep tissue pressure injury (DTPI) at the genetic level by analyzing microRNA (miRNA) expression profiles in DTPI tissues. Methods: A model of DTPI was established in 3 adult mice and 3 elderly mice, whereas another set of 3 adult mice and 3 elderly mice was used as controls. Wound tissues were stained with hematoxylin and eosin to observe the histologic changes, and total RNA was extracted for high-throughput sequencing. Differentially expressed oxidative stress-related miRNAs were screened, and target genes were predicted using TargetScan (v5.0) and Miranda (v3.3a). Enrichment analysis of these genes was executed using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. Selected differentially expressed miRNAs were further validated by quantitative real-time–polymerase chain reaction. Results: The results showed that 128 miRNAs were associated with oxidative stress, among which 86 were downregulated, and 42 were upregulated in the DTPI-elderly group; 21 were differentially expressed in the DTPI-adult group (P < 0.05). Moreover, the miRNA associated with oxidation stress between the two groups was miR-181a-1-3p. Its target genes mainly regulated MAPK and AGE pathways. quantitative real-time–polymerase chain reaction results showed that miR-181a-1-3p and miR-21a-5p were significantly downregulated in DTPI tissues. Conclusion: By analyzing miRNA expression profiles related to oxidative stress through a high-throughput sequencing system, this study sheds light on the potential pathologic mechanisms underpinning DTPI.

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“…Kuno et al demonstrated that elevated miR-125b expression from activated phagocytic monocytes is a genetic modi er related to anemia severity in β-thal patients 18 . El-Khazragy et al suggested that plasma dysregulated miR-let-7d, miR-122, and miR-200 serve as novel and non-invasive predictor biomarkers for cellular damage under condition of tissue iron excess in transfusion-dependent β-thal patients 19 .…”

Section: Discussionmentioning

confidence: 99%

Identification of deregulated circular RNA circ-0008102 as novel biomarker in pediatric β-thalassemia patients

Chen¹,

Pan

Zhang

et al. 2022

Preprint

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Circular RNA circ-0008102 has previously been found upregulated in β-thalassemia (β-thal) in circRNAs microarray. Our study aimed to identify whether circ-0008102 could be a novel biomarker in β-thal. qRT-PCR confirmed that the expression levels of circ-0008102 in pediatric β-thal patients with HbF ≥ 5.0% (n = 26) were significantly higher than that in pediatric β-thal patients with HbF < 5.0% (n = 33) and healthy controls (n = 30). ROC curves analysis showed that the AUC of circ-0008102 for differentiating patients with HbF ≥ 5.0% from patients with HbF < 5.0% and healthy controls with an AUC of 0.774 and 0.702, respectively. Furthermore, circ-0008102 expression was positively correlated with the levels of HbF, GGT, β-globin and γ-globin mRNA, but was negatively corrected with the levels of MCV, MCH, HbA and Cr. circ-0008102 was mainly located in the cytoplasm, and its five highest-ranking candidates miRNAs were miR-372-3p, miR-329-5p, miR-198, miR-152-5p and miR-627-3p. 651 mRNAs regulated by these miRNAs were found based on bioinformatics analysis, and enrichment analysis of circ-0008102/miRNAs/mRNAs network showed these mRNAs were involved in DNA binding and transcription regulatory region binding, and were associated with Th17 cell differentiation and stem cell pluripotency signaling pathways. In conclusion, we preliminary proved that peripheral blood deregulated circ-0008102 might be an effective biomarker for detection of pediatric β-thal with high HbF. circ-0008102 participates in the pathogenesis of β-thal through regulating γ-globin expression, which needs to be investigated further.

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Circulating miRNAs and tissue iron overload in transfusion-dependent β-thalassemia major: novel predictors and follow-up guide

Cited by 3 publications

References 46 publications

Peripheral blood circular RNA circ-0008102 may serve as a novel clinical biomarker in beta-thalassemia patients

Peripheral blood circular RNA circ-0008102 may serve as a novel clinical biomarker in beta-thalassemia patients

Analysis of microRNA expression profiles involved oxidative stress in a deep tissue pressure injury

Identification of deregulated circular RNA circ-0008102 as novel biomarker in pediatric β-thalassemia patients

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