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通过生物信息学分析鉴定颅内动脉瘤破裂的潜在核心基因

Identification of Potential Core Genes for the Rupture of Intracranial Aneurysms by a Bioinformatics Analysis.

作者信息

Lin Yuan, Ma Hai-Ying, Wang Yi, He Jiang, Liu Heng-Jian

机构信息

Changzhou Hospital of Traditional Chinese Medicine, Changzhou, China.

出版信息

Front Genet. 2022 Mar 30;13:875007. doi: 10.3389/fgene.2022.875007. eCollection 2022.

Abstract

Previous studies, using autopsy and angiography, have shown that 3.6-6% of the population have intracranial aneurysms, and the rupture of aneurysm can lead to brain dysfunction or even death in patients. To explore potential preventional target genes for the ruptured of aneurysm, we analyze three gene expression datasets (GSE13353, GSE15629 and GSE54083) derived from the GEO database. We confirm DEGs associated with the unrupture of aneurysms by R package. DAVID version provides functional classification and annotation analyses of associated genes, including GO and KEGG pathway. PPI of these DEGs is analyzed based on the string database and visualized by Cytoscape software. DEGs are verified by qRT-PCR using samples isolated from the patients. 249 overlapping DEGs, including 96 up-regulated genes and 153 down-regulated genes are screened using the Venn diagram webtool. The GO term and KEGG pathways analysis results indicate that these DEGs are mainly enriched in protein phosphorylation, apoptotic process and inflammatory response in the BP term and focal adhesion, thyroid hormone signaling pathway, ErbB signaling pathway, cytokine-cytokine receptor interaction and some disease processes in the KEGG pathways. 6 candidates are confirmed by Cytoscape software and qRT-PCR, including APP, JUN, GSK3B, ErbB2, PPBP and THBS1. Our data and previous studies show that ErbB2 and THBS1 are crucial to prevent aneurysm rupture, while APP, JUN, GSK3B and PPBP performs the opposite role, and further experiments are needed to verify these findings.

摘要

以往使用尸检和血管造影的研究表明,3.6% - 6%的人群患有颅内动脉瘤,动脉瘤破裂可导致患者脑功能障碍甚至死亡。为了探索动脉瘤破裂的潜在预防靶基因,我们分析了来自基因表达综合数据库(GEO数据库)的三个基因表达数据集(GSE13353、GSE15629和GSE54083)。我们通过R包确认了与动脉瘤未破裂相关的差异表达基因(DEGs)。DAVID版本提供了相关基因的功能分类和注释分析,包括基因本体(GO)和京都基因与基因组百科全书(KEGG)通路。基于STRING数据库分析这些DEGs的蛋白质 - 蛋白质相互作用(PPI),并通过Cytoscape软件进行可视化。使用从患者分离的样本通过定量逆转录 - 聚合酶链反应(qRT - PCR)验证DEGs。使用维恩图网络工具筛选出249个重叠的DEGs,包括96个上调基因和153个下调基因。GO术语和KEGG通路分析结果表明,这些DEGs主要在生物学过程(BP)术语中的蛋白质磷酸化、凋亡过程和炎症反应以及KEGG通路中的粘着斑、甲状腺激素信号通路、表皮生长因子受体2(ErbB)信号通路、细胞因子 - 细胞因子受体相互作用和一些疾病过程中富集。通过Cytoscape软件和qRT - PCR确认了6个候选基因,包括淀粉样前体蛋白(APP)、原癌基因蛋白c - Jun(JUN)、糖原合成酶激酶3β(GSK3B)、ErbB2、血小板碱性蛋白(PPBP)和凝血酶敏感蛋白1(THBS1)。我们的数据和以往研究表明,ErbB2和THBS1对预防动脉瘤破裂至关重要,而APP、JUN、GSK3B和PPBP则起相反作用,需要进一步实验来验证这些发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2280/9006073/e27a9412dc11/fgene-13-875007-g001.jpg

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