Expression profiles and potential clinical significance of circular RNAs in peripheral neutrophils of patients with intracranial atherosclerotic stenosis.

IF 4.8 4区 医学 Q3 CLINICAL NEUROLOGY
Brain Circulation Pub Date : 2025-07-03 eCollection Date: 2025-07-01 DOI:10.4103/bc.bc_16_24
Ziping Han, Tao Wang, Lingzhi Li, Junfen Fan, Rongliang Wang, Yangmin Zheng, Feng Yan, Haiping Zhao, Yumin Luo, Liqun Jiao
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引用次数: 0

Abstract

Background: Expression profiles and clinical significance of circular RNAs (circRNAs) in intracranial atherosclerotic stenosis (ICAS) patients have not been investigated yet.

Materials and methods: A circRNA microarray was employed to identify differentially expressed circRNAs (DEcircRNAs) in peripheral neutrophils of ICAS patients. The levels of upregulated hsa-circRNA-087631/hsa-circRNA-101141 and downregulated hsa-circRNA-100914/hsa-circRNA-001082 were verified using quantitative real-time polymerase chain reaction (qRT-PCR). In addition, we compared the levels of those four DEcircRNAs before endovascular treatment (pre-E) and 24 h after endovascular treatment (post-E) and between patients with adverse event and severe adverse event (AE/SAE) and those without. Their area under the curve from the receiver operating characteristic (ROC) curve was calculated as well. Bioinformatic analyses of DEcircRNAs host genes and targeted genes in DEcircRNA-miRNA-mRNA regulatory network were further performed.

Results: A total of 70 circRNAs were identified as differentially expressed in patients with ICAS; of these, 7 were upregulated and 63 were downregulated. qRT-PCR-based validation results of the four DEcircRNAs corresponded with the microarray data. The upregulated hsa-circRNA-087631 and hsa-circRNA-101141 were significantly downregulated 24 h post-E; moreover, they were significantly increased in patients with perioperative AE/SAE compared to those without AE/SAE. ROC analysis further supported their potential to be exploited as diagnostic biomarkers for ICAS. The validated DEcircRNA-miRNA-mRNA regulatory network and further bioinformatic analysis supported the core roles of hsa-circRNA-101141 in regulating target genes mainly related to actin or microtubule-based process.

Conclusions: DEcircRNAs in peripheral neutrophils could serve as biomarkers for the diagnostic and AE prediction in ICAS patients receiving endovascular treatment. Moreover, these DEcircRNAs, especially hsa-circRNA-101141-hsa-miRNA-181d axis, might participate in the pathogenesis of ICAS by acting on actin or microtubule-based cytoskeleton organization processes in neutrophils.

Trial registration: The CRTICAS study has been registered previously in the ClinicalTrial.gov database (NCT01994161).

颅内动脉粥样硬化性狭窄患者外周血中性粒细胞环状rna的表达谱及潜在临床意义。
背景:环状rna (circRNAs)在颅内动脉粥样硬化性狭窄(ICAS)患者中的表达谱及临床意义尚未得到研究。材料和方法:采用circRNA微阵列技术鉴定ICAS患者外周血中性粒细胞中差异表达的circRNAs (DEcircRNAs)。采用定量实时聚合酶链反应(qRT-PCR)验证hsa-circRNA-087631/hsa-circRNA-101141和下调的hsa-circRNA-100914/hsa-circRNA-001082的表达水平。此外,我们比较了血管内治疗前(e前)和血管内治疗后24小时(e后)以及不良事件和严重不良事件(AE/SAE)患者与无不良事件患者之间这四种DEcircRNAs的水平。同时计算受试者工作特征曲线下的面积。进一步对DEcircRNAs宿主基因和DEcircRNA-miRNA-mRNA调控网络中的靶基因进行生物信息学分析。结果:共有70个circrna在ICAS患者中被鉴定为差异表达;其中,7个上调,63个下调。四种decircrna的qrt - pcr验证结果与微阵列数据一致。上调的hsa-circRNA-087631和hsa-circRNA-101141在e后24 h显著下调;此外,围手术期AE/SAE患者与无AE/SAE患者相比,它们显著增加。ROC分析进一步支持了它们作为ICAS诊断生物标志物的潜力。经过验证的DEcircRNA-miRNA-mRNA调控网络和进一步的生物信息学分析支持了hsa-circRNA-101141在调控主要与肌动蛋白或微管过程相关的靶基因中的核心作用。结论:外周中性粒细胞DEcircRNAs可作为ICAS患者接受血管内治疗的诊断和AE预测的生物标志物。此外,这些decircrna,特别是hsa-circRNA-101141-hsa-miRNA-181d轴,可能通过作用于中性粒细胞中肌动蛋白或微管细胞骨架组织过程参与ICAS的发病过程。试验注册:CRTICAS研究先前已在ClinicalTrial.gov数据库(NCT01994161)中注册。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Brain Circulation
Brain Circulation Multiple-
自引率
5.30%
发文量
31
审稿时长
16 weeks
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