外周血环状 RNA circ-0008102 可作为β-地中海贫血患者的新型临床生物标志物。
Peripheral blood circular RNA circ-0008102 may serve as a novel clinical biomarker in beta-thalassemia patients.
机构信息
Medical Genetic Diagnosis and Therapy Center, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fujian Provincial Key Laboratory of Prenatal Diagnosis and Birth Defect, Fuzhou, 350001, China.
The School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, 350001, China.
出版信息
Eur J Pediatr. 2024 Mar;183(3):1367-1379. doi: 10.1007/s00431-023-05398-y. Epub 2024 Jan 2.
UNLABELLED
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.
目的
circ-0008102 在β-地中海贫血（β-thal）的 circRNAs 微阵列（GSE196682 和 GSE241141）中存在失调。本研究旨在确定 circ-0008102 是否可以成为β-thal 的新型生物标志物。
方法
选择儿科β-thal 患者（无输血 n=39，有输血 n=20）和健康对照者（n=30）的外周血。采用 qRT-PCR、ROC 曲线分析、Spearman 相关性分析和 FISH 分析 circ-0008102 的临床价值。
结果
qRT-PCR 证实无输血的儿科β-thal 患者的 circ-0008102 表达明显升高。ROC 曲线分析显示，区分无输血和有输血患者以及健康对照者的 circ-0008102 的 AUC 为 0.733 和 0.711。此外，circ-0008102 的表达与 RBC、HbF、β-球蛋白和γ-球蛋白 mRNA 的水平呈正相关，与 HbA 和 Cr 的水平呈负相关。circ-0008102 主要位于细胞质中。circ-0008102 可诱导γ-球蛋白激活，并负调控 K562 细胞中五个排名最高的候选 miRNA（miR-372-3p、miR-329-5p、miR-198、miR-152-5p 和 miR-627-3p）的表达。
结论
我们证明外周血上调的 circ-0008102 可能是无输血儿科β-thal 的新型临床生物标志物。
已知情况
• circRNAs 已知参与多种人类疾病，一些 circRNAs 被认为是β-thal 检测的一类有前途的基于血液的生物标志物。• circRNAs 通过表观遗传修饰和基因表达调控发挥生物学功能，β-thal 中失调的 circRNAs 可能参与β-thal 中 HbF 的诱导。
新发现
• 外周血 circ-0008102 可能是无输血儿科β-thal 的新型临床生物标志物。• circ-0008102 通过调节γ-球蛋白的表达参与β-thal 的发病机制，并负调控 miR-372-3p、miR-329-5p、miR-198、miR-152-5p 和 miR-627-3p 的表达。
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