外周环状rna hsa_circ_0075436和hsa_circ_0005729作为急性缺血性卒中的诊断和预后生物标志物:表达谱和机制见解

IF 3.9 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Frontiers in Molecular Biosciences Pub Date : 2025-10-01 eCollection Date: 2025-01-01 DOI:10.3389/fmolb.2025.1657284
Wenqun Jiang, Weidong Chen, Shihao Lin, Pinpin Hou, Yichao Jin, Xiaohua Zhang, Hui Wu, Li Gao, Qin Hu
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引用次数: 0

摘要

环状rna (circRNAs)是一类稳定、保守和组织特异性的非编码rna,已显示出作为急性缺血性卒中(AIS)诊断和预后生物标志物的潜力。然而,它们在外周血单个核细胞(PBMCs)中的表达和功能作用在很大程度上仍未被探索。方法:我们对来自AIS患者(n = 5)和匹配的健康对照(n = 5)的PBMC样本进行了全转录组RNA测序。在验证队列(n = 60)中,通过qRT-PCR验证了前10个差异表达的circrna,并在更大的复制队列(n = 288)中进一步验证了两个持续失调的circrna。通过功能富集分析和竞争内源RNA (ceRNA)网络构建来探索潜在的调控机制。结果:两种circrna hsa_circ_0075436和hsa_circ_0005729在AIS患者的pbmc中显著降低。在入院和出院时,表达水平与NIH脑卒中量表(NIHSS)得分呈负相关。受试者工作特征(ROC)曲线分析显示其诊断效果较好。生物信息学分析和qRT-PCR进一步表明,hsa_circ_0005729可能通过hsa-miR-1301/COL1A1轴影响AIS的血脑屏障破坏和外周免疫抑制。结论:Hsa_circ_0075436和hsa_circ_0005729是有希望用于AIS诊断和预后的pbmc衍生生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Peripheral circular RNAs hsa_circ_0075436 and hsa_circ_0005729 as diagnostic and prognostic biomarkers in acute ischemic stroke: expression profiles and mechanistic insights.

Introduction: Circular RNAs (circRNAs) are a class of stable, conserved, and tissue-specific non-coding RNAs that have shown potential as diagnostic and prognostic biomarkers in acute ischemic stroke (AIS). However, their expression and functional roles in peripheral blood mononuclear cells (PBMCs) remain largely unexplored.

Methods: We performed whole transcriptome RNA sequencing on PBMC samples from AIS patients (n = 5) and matched healthy controls (n = 5). The top 10 differentially expressed circRNAs were validated by qRT-PCR in a validation cohort (n = 60), and two consistently dysregulated circRNAs were further validated in a larger replication cohort (n = 288). Functional enrichment analysis and competing endogenous RNA (ceRNA) network construction were conducted to explore potential regulatory mechanisms.

Results: Two circRNAs, hsa_circ_0075436 and hsa_circ_0005729, significantly decreased in PBMCs of AIS patients. The expressive levels negatively correlated with NIH Stroke Scale (NIHSS) scores at admission and discharge. Receiver operating characteristic (ROC) curve analysis demonstrated their strong diagnostic performance. Bioinformatics analyses and qRT-PCR further suggested that hsa_circ_0005729 may influence BBB disruption and peripheral immune suppression in AIS via hsa-miR-1301/COL1A1 axis.

Conclusion: Hsa_circ_0075436 and hsa_circ_0005729 are promising PBMC-derived biomarkers for the diagnosis and prognosis of AIS.

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来源期刊
Frontiers in Molecular Biosciences
Frontiers in Molecular Biosciences Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
7.20
自引率
4.00%
发文量
1361
审稿时长
14 weeks
期刊介绍: Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology. Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life. In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.
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