结合孟德尔随机分析和网络毒理学策略，确定环境污染物与胶质母细胞瘤的因果关系和内在机制：对 4-羟基苯甲酸甲酯的研究。

IF 6.2 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Ecotoxicology and Environmental Safety Pub Date : 2024-11-15 DOI:10.1016/j.ecoenv.2024.117311

Haimin Song , Huaiyu Zhou , Shaochun Yang , Chunming He

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引用次数: 0

摘要

背景：越来越多的环境污染物与人类疾病相关。我们探讨了芳香族小分子--4-羟基苯甲酸甲酯（MEP）导致胶质母细胞瘤（GBM）发病的机制：方法：通过孟德尔随机化（MR）分析确定了MEP与GBM的因果关系。我们通过整合 GBM 的靶点、GEO 的差异表达基因（DEGs）和 MEP 的靶点基因，确定了关键靶点。中枢基因网络由 STRING 和 Cytoscape 工具获得，GO、KEGG 富集分析由 clusterProfiler R 软件包完成。通过Autodock软件对这些中心靶点进行了分子对接：结果：MEP作为风险因素与GBM存在因果关系（P < 0.05，OR > 1）。得出了46个关键靶点，其中CASP3、MMP2和CDK4被筛选为中心靶点。分子对接分析表明，MEP与CASP3、MMP2、CDK4、CASP8和MCL1之间具有良好的结合能力：结论：MEP与GBM之间存在因果关系。CASP3、MMP2、CDK4、CASP8 和 MCL1 被确定为与 GBM 相关的关键靶点。这一发现可能为我们深入了解环境污染物是如何导致 GBM 的发展提供了重要依据。

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Combining mendelian randomization analysis and network toxicology strategy to identify causality and underlying mechanisms of environmental pollutants with glioblastoma: A study of Methyl-4-hydroxybenzoate

Background

An increasing number of environmental pollutants are associated with human diseases. We explored the mechanisms by which an aromatic small molecule -- Methyl-4-hydroxybenzoate (MEP) contribute to the development of glioblastoma (GBM).

Methods

The causality of MEP and GBM were identified via the Mendelian Randomization (MR) analysis. We identified the key targets by integrating the targets of GBM, differential expressed genes (DEGs) from GEO and target genes of MEP. The network of hub genes was obtained from STRING and Cytoscape tools and GO, KEGG enrichment analysis were conducted by clusterProfiler R package. These hub targets were executed molecular docking via Autodock software.

Results

MEP had a causal association with GBM as risk factors (P < 0.05, OR > 1). 46 key targets were derived, in which CASP3, MMP2 and CDK4 were screened as the hub targets. MEP might play a role in the GBM by affecting the pathways of neuroactive ligand-receptor interaction, Molecular docking analysis showed a good binding ability of between MEP and CASP3, MMP2, CDK4, CASP8 and MCL1.

Conclusions

A causal relationship between MEP and GBM exists. CASP3, MMP2, CDK4, CASP8 and MCL1 have been identified as the crucial targets correlating with GBM. This discovery may provide an important insight into how environmental pollutants contribute to the development of GBM.

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来源期刊

Ecotoxicology and Environmental Safety 环境科学-毒理学

CiteScore

12.10

自引率

5.90%

发文量

1234

审稿时长

88 days

期刊介绍： Ecotoxicology and Environmental Safety is a multi-disciplinary journal that focuses on understanding the exposure and effects of environmental contamination on organisms including human health. The scope of the journal covers three main themes. The topics within these themes, indicated below, include (but are not limited to) the following: Ecotoxicology、Environmental Chemistry、Environmental Safety etc.