Bioinformatics analysis of differentially expressed genes related to ischemia and hypoxia in spinal cord injury and construction of miRNA-mRNA or mRNA-transcription factor interaction network.

IF 3.2 4区医学 Q1 Pharmacology, Toxicology and Pharmaceutics

Toxicology Mechanisms and Methods Pub Date : 2024-03-01 Epub Date: 2024-01-03 DOI:10.1080/15376516.2023.2286363

Lijuan Zhu, Na Gao, Zhibo Zhu, Shiping Zhang, Xi Li, Jing Zhu

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Abstract

Background: Previous studies show that spinal cord ischemia and hypoxia is an important cause of spinal cord necrosis and neurological loss. Therefore, the study aimed to identify genes related to ischemia and hypoxia after spinal cord injury (SCI) and analyze their functions, regulatory mechanism, and potential in regulating immune infiltration.

Methods: The expression profiles of GSE5296, GSE47681, and GSE217797 were downloaded from the Gene Expression Omnibus database. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to determine the function and pathway enrichment of ischemia- and hypoxia-related differentially expressed genes (IAHRDEGs) in SCI. LASSO model was constructed, and support vector machine analysis was used to identify key genes. The diagnostic values of key genes were evaluated using decision curve analysis and receiver operating characteristic curve analysis. The interaction networks of miRNAs-IAHRDEGs and IAHRDEGs-transcription factors were predicted and constructed with the ENCORI database and Cytoscape software. CIBERSORT algorithm was utilized to analyze the correlation between key gene expression and immune cell infiltration.

Results: There were 27 IAHRDEGs identified to be significantly expressed in SCI at first. These genes were mostly significantly enriched in wound healing function and the pathway associated with lipid and atherosclerosis. Next, five key IAHRDEGs (Abca1, Casp1, Lpl, Procr, Tnfrsf1a) were identified and predicted to have diagnostic value. Moreover, the five key genes are closely related to immune cell infiltration.

Conclusion: Abca1, Casp1, Lpl, Procr, and Tnfrsf1a may promote the pathogenesis of ischemic or hypoxic SCI by regulating vascular damage, inflammation, and immune infiltration.

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脊髓损伤缺血缺氧相关差异表达基因的生物信息学分析及miRNA-mRNA或mrna -转录因子相互作用网络的构建。

背景:已有研究表明，脊髓缺血缺氧是导致脊髓坏死和神经功能丧失的重要原因。因此，本研究旨在鉴定脊髓损伤(SCI)后缺血缺氧相关基因，分析其功能、调控机制及其在免疫浸润调节中的潜力。方法:从Gene expression Omnibus数据库下载GSE5296、GSE47681和GSE217797的表达谱。通过基因本体论和京都基因与基因组百科分析来确定缺血和缺氧相关差异表达基因(IAHRDEGs)在SCI中的功能和通路富集。构建LASSO模型，利用支持向量机分析方法识别关键基因。采用决策曲线分析和受者工作特征曲线分析评价关键基因的诊断价值。利用ENCORI数据库和Cytoscape软件预测并构建miRNAs-IAHRDEGs和iahrdegs -转录因子的相互作用网络。利用CIBERSORT算法分析关键基因表达与免疫细胞浸润的相关性。结果:有27个iahrdeg首次在脊髓损伤中显著表达。这些基因大多在伤口愈合功能和脂质及动脉粥样硬化相关通路中显著富集。接下来，鉴定出5个关键iahrdeg (Abca1、Casp1、Lpl、Procr、Tnfrsf1a)并预测其具有诊断价值。此外，这五个关键基因与免疫细胞浸润密切相关。结论:Abca1、Casp1、Lpl、Procr和Tnfrsf1a可能通过调节血管损伤、炎症和免疫浸润促进缺血性或缺氧性脊髓损伤的发生。

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来源期刊

Toxicology Mechanisms and Methods 医学-毒理学

CiteScore

6.60

自引率

3.10%

发文量

审稿时长

6-12 weeks

期刊介绍： Toxicology Mechanisms and Methods is a peer-reviewed journal whose aim is twofold. Firstly, the journal contains original research on subjects dealing with the mechanisms by which foreign chemicals cause toxic tissue injury. Chemical substances of interest include industrial compounds, environmental pollutants, hazardous wastes, drugs, pesticides, and chemical warfare agents. The scope of the journal spans from molecular and cellular mechanisms of action to the consideration of mechanistic evidence in establishing regulatory policy. Secondly, the journal addresses aspects of the development, validation, and application of new and existing laboratory methods, techniques, and equipment. A variety of research methods are discussed, including: In vivo studies with standard and alternative species In vitro studies and alternative methodologies Molecular, biochemical, and cellular techniques Pharmacokinetics and pharmacodynamics Mathematical modeling and computer programs Forensic analyses Risk assessment Data collection and analysis.