用生物信息学分析鉴定与脑出血相关的潜在生物标志物和小分子化合物。

IF 1.4 4区 医学 Q4 NEUROSCIENCES
Ziqi Yang, Ruonan Wang, Xingyu Chen, Dexi Zhao
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引用次数: 1

摘要

本研究旨在进一步探讨颅内出血(ICH)的潜在分子机制,对含血周组织、对侧灰质和白质的基因表达谱GSE24265进行检索和分析。将数据分层聚类,筛选差异表达基因(DEGs)。对DEG枢纽进行功能分析和蛋白相互作用分析,并构建miRNA -转录因子(TF)靶点网络。此外,候选的小分子化合物可能逆转ICH相关基因的表达,并通过CMap鉴定。该方法共发现408个deg。确定了趋化因子相关、抗原免疫相关、病原体感染、细胞反应、酪氨酸磷酸化和MAPK级联正调控等5个模块。在蛋白-蛋白相互作用(PPI)网络中获得的前10个枢纽基因中,CCL5、CXCL8、ICAM1、IL-1B、IL-6、VCAM1和VEGFA的表达水平与ICH相关。共获得237个miRNA - TF靶调控关系,包括6个TF、11个miRNA和105个靶基因。最后,CMap数据库确定Prestwick-1083、沙莫特罗、异环磷酰胺、甲基多巴胺、硝呋替莫、心得安和甲氧苄胺是脑出血的潜在治疗药物,而阿霉素、美萘醌和阿扎胞苷可能会增加脑出血的致病性。此外,CCL5、CXCL8和VEGFA可能是ICH新的候选易感基因。包括沙莫特罗在内的一些小分子药物可用于治疗脑出血。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identification of potential biomarkers and small‑molecule compounds related to intracerebral hemorrhage with bioinformatics analysis.

This study aimed to further explore the underlying molecular mechanism of intracerebral hemorrhage (ICH), gene expression profile GSE24265, containing perihematomal tissues, contralateral grey and white matters were retrieved and analyzed. The data was hierarchically clustered and the differentially expressed genes (DEGs) were screened. Functional analysis and protein interaction analysis of DEG hubs were performed, and the miRNA‑transcription factor (TF)‑target network was built. In addition, the candidate small-molecule compounds that might reverse the expression of an ICH‑linked gene were identified by CMap. This method revealed a total of 408 DEGs. Five modules including chemokinerelated, antigen immune-related, pathogen infection, cell reaction, and positive regulation of tyrosine phosphorylation and MAPK cascade were identified. The expression levels of CCL5, CXCL8, ICAM1, IL-1B, IL-6, VCAM1, and VEGFA were correlated with ICH among the top 10 hub genes obtained in the protein-protein interaction (PPI) network. A total of 237 miRNA‑TF‑target regulatory relationships were obtained, including 6 TFs, 11 miRNAs and 105 target genes. Finally, the CMap database identified Prestwick-1083, xamoterol, ifosfamide, methyldopate, nifurtimox, propranolol, and methoxamine as potential therapeutic agents for ICH while doxorubicin, menadione and azacitidine may increase its pathogenicity. Furthermore, CCL5, CXCL8 and VEGFA may be novel candidate susceptibility genes for ICH. Some small-molecule drugs, including xamoterol may be used for the treatment of ICH.

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来源期刊
CiteScore
2.20
自引率
7.10%
发文量
40
审稿时长
>12 weeks
期刊介绍: Acta Neurobiologiae Experimentalis (ISSN: 0065-1400 (print), eISSN: 1689-0035) covers all aspects of neuroscience, from molecular and cellular neurobiology of the nervous system, through cellular and systems electrophysiology, brain imaging, functional and comparative neuroanatomy, development and evolution of the nervous system, behavior and neuropsychology to brain aging and pathology, including neuroinformatics and modeling.
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