Circulating PIWI-interacting RNAs in Acute Ischemic Stroke patients

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research Pub Date : 2025-01-15 DOI:10.1016/j.ncrna.2025.01.005

Salman M. Toor , Eman K. Aldous , Aijaz Parray , Naveed Akhtar , Yasser Al-Sarraj , Abdelilah Arredouani , Ghulam Jeelani Pir , Sajitha V. Pananchikkal , Omar El-Agnaf , Ashfaq Shuaib , Nehad M. Alajez , Omar M.E. Albagha

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引用次数: 0

Abstract

Background

Stroke refers to an abrupt neurological deficit, caused by an acute focal injury of the central nervous system via infarction or hemorrhage due to impaired vascularity, and remains among the leading causes of disability and death worldwide. Stroke is often preceded by an episode of neuronal deficit termed transient ischemic attack (TIA), which presents an effective opportunity for mitigating the risk of an eminent acute ischemic stroke (AIS). Circulating non-coding RNAs (ncRNAs) have emerged as important biomarkers for stroke, but PIWI-interacting RNAs (piRNAs), a class of small regulatory ncRNAs, have not been previously explored as diagnostic or prognostic biomarkers for stroke.

Methods

We conducted comprehensive circulating piRNA profiling of AIS and TIA patients using RNA-seq on serum samples collected within 24 h of clinical diagnosis. The study cohort was divided into discovery and cross-validation datasets to identify replicated piRNAs using stringent analysis cut-offs. The expression levels of the panel of differentially regulated piRNAs between AIS and TIA patients were also compared with healthy controls.

Results

We identified a panel of 10 differentially regulated piRNAs between AIS and TIA patients; hsa-piR-28272, -piR-32972, -piR-28247, -piR-24553, -piR-24552, -piR-28275, -piR-28707 and -piR-32882 were upregulated, while hsa-piR-23058 and -piR-23136 were downregulated in AIS patients. Moreover, these 10 piRNAs were also differentially expressed in AIS patients compared to healthy controls. In addition, we investigated the potential gene targets of the dysregulated piRNAs and their plausible involvement in pathophysiological processes affected in stroke.

Conclusions

The imbalances in the circulating piRnome of AIS and TIA patients presented herein provide important insights into the roles of piRNAs following ischemic brain injury and potentially provide opportunities to mitigate stroke-induced mortality and morbidity.

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急性缺血性卒中患者循环piwi相互作用rna

背景：中风是指由中枢神经系统急性局灶性损伤引起的突发性神经功能缺损，由血管受损引起的梗死或出血引起，是世界范围内致残和死亡的主要原因之一。中风之前通常会出现一段称为短暂性脑缺血发作（TIA）的神经元缺陷，这为减轻急性脑缺血发作（AIS）的风险提供了一个有效的机会。循环非编码rna （ncrna）已成为中风的重要生物标志物，但piwi相互作用rna （pirna）是一类小的调节性ncrna，以前尚未被探索作为中风的诊断或预后生物标志物。方法对AIS和TIA患者临床诊断后24 h内采集的血清样本采用RNA-seq法进行循环piRNA谱分析。研究队列分为发现和交叉验证数据集，使用严格的分析切断来识别复制的pirna。还比较了AIS和TIA患者之间差异调节的pirna组的表达水平。我们确定了AIS和TIA患者之间的10个差异调节pirna；hsa-piR-28272、-piR-32972、-piR-28247、-piR-24553、-piR-24552、-piR-28275、-piR-28707和-piR-32882在AIS患者中表达上调，而hsa-piR-23058和-piR-23136表达下调。此外，与健康对照组相比，这10种pirna在AIS患者中的表达也存在差异。此外，我们还研究了失调pirna的潜在基因靶点及其在卒中病理生理过程中的可能参与。结论AIS和TIA患者循环pirna的失衡为缺血性脑损伤后pirna的作用提供了重要的见解，并可能为降低卒中引起的死亡率和发病率提供了机会。

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

Non-coding RNA Research Medicine-Biochemistry (medical)

CiteScore

7.70

自引率

6.00%

发文量

审稿时长

49 days

期刊介绍： Non-coding RNA Research aims to publish high quality research and review articles on the mechanistic role of non-coding RNAs in all human diseases. This interdisciplinary journal will welcome research dealing with all aspects of non-coding RNAs-their biogenesis, regulation and role in disease progression. The focus of this journal will be to publish translational studies as well as well-designed basic studies with translational and clinical implications. The non-coding RNAs of particular interest will be microRNAs (miRNAs), small interfering RNAs (siRNAs), small nucleolar RNAs (snoRNAs), U-RNAs/small nuclear RNAs (snRNAs), exosomal/extracellular RNAs (exRNAs), Piwi-interacting RNAs (piRNAs) and long non-coding RNAs. Topics of interest will include, but not limited to: -Regulation of non-coding RNAs -Targets and regulatory functions of non-coding RNAs -Epigenetics and non-coding RNAs -Biological functions of non-coding RNAs -Non-coding RNAs as biomarkers -Non-coding RNA-based therapeutics -Prognostic value of non-coding RNAs -Pharmacological studies involving non-coding RNAs -Population based and epidemiological studies -Gene expression / proteomics / computational / pathway analysis-based studies on non-coding RNAs with functional validation -Novel strategies to manipulate non-coding RNAs expression and function -Clinical studies on evaluation of non-coding RNAs The journal will strive to disseminate cutting edge research, showcasing the ever-evolving importance of non-coding RNAs in modern day research and medicine.