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miRNA 表达谱分析显示微小 RNA-148b-3p 在蛛网膜下腔出血后脑血管痉挛中的潜在作用。

MiRNA expression profiling reveals a potential role of microRNA-148b-3p in cerebral vasospasm in subarachnoid hemorrhage.

机构信息

Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA.

Mass General Brigham Personalized Medicine, Mass General Brigham, Cambridge, MA, USA.

出版信息

Sci Rep. 2024 Sep 29;14(1):22539. doi: 10.1038/s41598-024-73579-2.

Abstract

Cerebral vasospasm (CVS) is an important contributor to delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage (aSAH), leading to high morbidity and long-term disability. While several microRNAs (miRNAs) have been implicated in vasospasm, the underlying mechanisms for CVS remain poorly understood. Our study aims to identify miRNAs that may contribute to the development of CVS. Whole-blood samples were obtained during or outside of vasospasm from aSAH patients whose maximal vasospasm was moderate or severe. MiRNAs were isolated from serial whole-blood samples, and miRNA sequencing was performed. Differentially expressed miRNAs were identified and the expression levels in patients' samples were verified using real-time qPCR. The biological functions of identified miRNA were evaluated in human brain endothelial cells (HBECs). MiRNA profiling revealed significant upregulation of miR-148b-3p in patients during CVS. We demonstrated that miR-148b-3p directly targeted and decreased the expression of ROCK1, affecting cell proliferation, migration, and invasion of HBECs through the ROCK-LIMK-Cofilin pathway. We propose that the upregulation of miRNA-148b-3p plays a role in the development of CVS by regulating actin cytoskeletal dynamics in HBECs, which is crucial for vascular function. Our study highlights miR-148b-3p as a potential diagnostic marker as well as therapeutic target for CVS following aSAH.

摘要

脑血管痉挛(Cerebral Vasospasm,CVS)是蛛网膜下腔出血(Aneurysmal Subarachnoid Hemorrhage,aSAH)后迟发性脑缺血的重要原因,导致高发病率和长期残疾。虽然有几种 microRNAs(miRNAs)被认为与血管痉挛有关,但 CVS 的潜在机制仍知之甚少。我们的研究旨在确定可能导致 CVS 发展的 miRNAs。在 aSAH 患者的血管痉挛期间或之外获得全血样本,其最大血管痉挛为中度或重度。从连续的全血样本中分离出 miRNAs,并进行 miRNA 测序。鉴定差异表达的 miRNAs,并使用实时 qPCR 验证患者样本中的表达水平。评估鉴定出的 miRNA 在人脑内皮细胞(HBECs)中的生物学功能。miRNA 谱分析显示,在 CVS 期间患者的 miR-148b-3p 显著上调。我们证明 miR-148b-3p 可以直接靶向并降低 ROCK1 的表达,通过 ROCK-LIMK-Cofilin 通路影响 HBECs 的细胞增殖、迁移和侵袭。我们提出,miR-148b-3p 的上调通过调节 HBECs 中的肌动蛋白细胞骨架动力学在 CVS 的发展中发挥作用,这对血管功能至关重要。我们的研究强调了 miR-148b-3p 作为 aSAH 后 CVS 的潜在诊断标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9985/11438990/4e9021f8e2eb/41598_2024_73579_Fig1_HTML.jpg

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