缺血性中风患者血小板相关基因的分析与调控机制

IF 3.6 4区 医学 Q3 CELL BIOLOGY Cellular and Molecular Neurobiology Pub Date : 2024-01-04 DOI:10.1007/s10571-023-01433-6
Yuan Li, Yuanlu Shu, Kun Yu, Ruihan Ni, Lan Chu
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引用次数: 0

摘要

研究发现,缺血性中风(IS)与血小板活性异常和血栓形成有关。然而,血小板相关基因(PRGs)在 IS 中的潜在意义仍有待进一步深入研究。本研究从基因表达总库(GEO)数据库中提取了与IS相关的转录组数据集。将差异表达基因(DEGs)、IS相关模块基因和PRGs交叉得到目标基因,并通过两种机器学习算法筛选出IS的关键基因。构建了基于关键基因的诊断模型。针对 IS 的关键基因进行了基因组富集分析(GSEA)和免疫微环境分析。构建了共表达、TF-mRNA和竞争性内源性RNA(ceRNA)调控网络,以揭示关键基因的潜在调控。同时还预测了针对关键基因的潜在药物。共获得 8 个与免疫相关功能有关的靶基因。获得的四个血小板相关关键基因与免疫和能量代谢有关。通过实时定量聚合酶链反应(qRT-PCR)测定了 DOCK8、GIMAP5 和 ICOS 的异常表达,并确定了这些关键基因之间的显著相关性。值得注意的是,hsa-miR-17-3p、hsa-miR-3158-3p、hsa-miR-423-3p 和 hsa-miR-193a-8p 可同时调控所有关键基因。此外,咖啡因、卡铂和沃普替利单抗是这些关键基因的靶向药物。本研究发现了四个与血小板相关的IS关键基因,这可能有助于加深对血小板相关基因在IS分子机制中作用的认识。
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Analysis and Regulatory Mechanisms of Platelet-Related Genes in Patients with Ischemic Stroke.

It was found that ischemic stroke (IS) was associated with abnormal platelet activity and thrombosis. However, the potential significance of platelet-related genes (PRGs) in IS still needs to be more thorough. This study extracted IS-related transcriptome datasets from the Gene Expression Omnibus (GEO) database. The target genes were obtained by intersecting the differentially expressed genes (DEGs), the module genes related to IS, and PRGs, where the key genes of IS were screened by two machine learning algorithms. The key genes-based diagnostic model was constructed. Gene set enrichment analysis (GSEA) and the immune microenvironment analyses were analyzed targeting key genes in IS. The co-expression, TF-mRNA, and competitive endogenous RNAs (ceRNA) regulatory networks were constructed to reveal the potential regulation of key genes. Potential drugs targeting key genes were predicted as well. Totals of eight target genes were obtained and were associated with immune-related functions. Four platelet-related key genes were acquired, which were related to immunity and energy metabolism. The abnormal expressions of DOCK8, GIMAP5, ICOS were determined by the quantitative real-time polymerase chain reaction (qRT-PCR), and the significant correlations among these key genes were identified. Notably, hsa-miR-17-3p, hsa-miR-3158-3p, hsa-miR-423-3p, and hsa-miR-193a-8p could regulate all key genes at the same time. In addition, Caffeine, Carboplatin, and Vopratelimab were the targeted drugs of these key genes. This study identified four platelet-related key genes of IS, which might help to deepen the understanding of the role of platelet-related genes in the molecular mechanism of IS.

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来源期刊
CiteScore
7.70
自引率
0.00%
发文量
137
审稿时长
4-8 weeks
期刊介绍: Cellular and Molecular Neurobiology publishes original research concerned with the analysis of neuronal and brain function at the cellular and subcellular levels. The journal offers timely, peer-reviewed articles that describe anatomic, genetic, physiologic, pharmacologic, and biochemical approaches to the study of neuronal function and the analysis of elementary mechanisms. Studies are presented on isolated mammalian tissues and intact animals, with investigations aimed at the molecular mechanisms or neuronal responses at the level of single cells. Cellular and Molecular Neurobiology also presents studies of the effects of neurons on other organ systems, such as analysis of the electrical or biochemical response to neurotransmitters or neurohormones on smooth muscle or gland cells.
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