解读苯并[a]芘在胶质母细胞瘤中的致癌作用：来自网络毒理学、单细胞转录组学和孟德尔随机化的见解。

IF 6.1 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Ecotoxicology and Environmental Safety Pub Date : 2025-10-01 DOI:10.1016/j.ecoenv.2025.119155

Liye Yi , Wencai Wang , Zhonghua Sun , Yinuo Chen , Zijie Xiong , Luyao Ma , Wei Ye , Xianfeng Li

{"title":"解读苯并[a]芘在胶质母细胞瘤中的致癌作用：来自网络毒理学、单细胞转录组学和孟德尔随机化的见解。","authors":"Liye Yi , Wencai Wang , Zhonghua Sun , Yinuo Chen , Zijie Xiong , Luyao Ma , Wei Ye , Xianfeng Li","doi":"10.1016/j.ecoenv.2025.119155","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Benzo[<em>a</em>]pyrene (BaP) is a known environmental carcinogen linked to multiple tumors, but its role in glioblastoma (GBM) remains poorly understood. This study aimed to explore BaP’s tumorigenic mechanisms in GBM through an integrated approach combining network toxicology, single-cell transcriptomics, Mendelian randomization, and bibliometric analysis.</div></div><div><h3>Methods</h3><div>BaP target genes were predicted using ChEMBL, SEA, and PharmMapper, and GBM-related genes were retrieved from GeneCards, OMIM, and TTD. Overlapping genes were used to construct a protein–protein interaction network in Cytoscape. Molecular docking and molecular dynamics simulations were performed to assess BaP–target interactions. Single-cell RNA-seq data (GSE131928) were analyzed to profile gene expression in GBM subpopulations. Mendelian randomization assessed causal relationships between core genes and GBM risk, and findings were validated in vitro. Bibliometric analysis tracked research trends on these genes.</div></div><div><h3>Results</h3><div>31 overlapping genes were identified. TP53 was highly expressed in MES-like and AC-like malignant cells as well as CD8⁺ Tex cells. MR revealed a significant inverse association between TP53 expression and GBM risk (OR = 0.13, 95 % CI: 0.04–0.47, p = 0.002). Docking and simulation showed strong BaP–TP53 binding, confirmed by in vitro experiments. Bibliometrics indicated that TP53 research in GBM has shifted from basic mechanisms to clinical translation.</div></div><div><h3>Conclusion</h3><div>BaP may drive GBM by targeting TP53, offering insights for GBM prevention and therapy.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"304 ","pages":"Article 119155"},"PeriodicalIF":6.1000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Deciphering the carcinogenic role of benzo[a]pyrene in glioblastoma: Insights from network toxicology, single-cell transcriptomics, and Mendelian randomization\",\"authors\":\"Liye Yi , Wencai Wang , Zhonghua Sun , Yinuo Chen , Zijie Xiong , Luyao Ma , Wei Ye , Xianfeng Li\",\"doi\":\"10.1016/j.ecoenv.2025.119155\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Benzo[<em>a</em>]pyrene (BaP) is a known environmental carcinogen linked to multiple tumors, but its role in glioblastoma (GBM) remains poorly understood. This study aimed to explore BaP’s tumorigenic mechanisms in GBM through an integrated approach combining network toxicology, single-cell transcriptomics, Mendelian randomization, and bibliometric analysis.</div></div><div><h3>Methods</h3><div>BaP target genes were predicted using ChEMBL, SEA, and PharmMapper, and GBM-related genes were retrieved from GeneCards, OMIM, and TTD. Overlapping genes were used to construct a protein–protein interaction network in Cytoscape. Molecular docking and molecular dynamics simulations were performed to assess BaP–target interactions. Single-cell RNA-seq data (GSE131928) were analyzed to profile gene expression in GBM subpopulations. Mendelian randomization assessed causal relationships between core genes and GBM risk, and findings were validated in vitro. Bibliometric analysis tracked research trends on these genes.</div></div><div><h3>Results</h3><div>31 overlapping genes were identified. TP53 was highly expressed in MES-like and AC-like malignant cells as well as CD8⁺ Tex cells. MR revealed a significant inverse association between TP53 expression and GBM risk (OR = 0.13, 95 % CI: 0.04–0.47, p = 0.002). Docking and simulation showed strong BaP–TP53 binding, confirmed by in vitro experiments. Bibliometrics indicated that TP53 research in GBM has shifted from basic mechanisms to clinical translation.</div></div><div><h3>Conclusion</h3><div>BaP may drive GBM by targeting TP53, offering insights for GBM prevention and therapy.</div></div>\",\"PeriodicalId\":303,\"journal\":{\"name\":\"Ecotoxicology and Environmental Safety\",\"volume\":\"304 \",\"pages\":\"Article 119155\"},\"PeriodicalIF\":6.1000,\"publicationDate\":\"2025-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Ecotoxicology and Environmental Safety\",\"FirstCategoryId\":\"93\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0147651325015003\",\"RegionNum\":2,\"RegionCategory\":\"环境科学与生态学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENVIRONMENTAL SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Ecotoxicology and Environmental Safety","FirstCategoryId":"93","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0147651325015003","RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENVIRONMENTAL SCIENCES","Score":null,"Total":0}

引用次数: 0

摘要

背景：苯并[a]芘（BaP）是一种已知的与多种肿瘤相关的环境致癌物，但其在胶质母细胞瘤（GBM）中的作用仍知之甚少。本研究旨在通过结合网络毒理学、单细胞转录组学、孟德尔随机化和文献计量学分析的综合方法，探讨BaP在GBM中的致瘤机制。方法：使用ChEMBL、SEA和PharmMapper预测BaP靶基因，并从GeneCards、OMIM和TTD中检索gbm相关基因。在Cytoscape中，利用重叠基因构建蛋白-蛋白相互作用网络。通过分子对接和分子动力学模拟来评估bap -靶标相互作用。分析单细胞RNA-seq数据（GSE131928）以分析GBM亚群中的基因表达。孟德尔随机化评估了核心基因与GBM风险之间的因果关系，并在体外验证了研究结果。文献计量分析追踪了这些基因的研究趋势。结果：共鉴定出31个重叠基因。TP53在mes样和ac样恶性细胞以及CD8 + Tex细胞中高表达。MR显示TP53表达与GBM风险呈显著负相关（OR = 0.13, 95 % CI: 0.04-0.47, p = 0.002）。对接模拟显示，BaP-TP53结合较强，体外实验也证实了这一点。文献计量学表明，TP53在GBM中的研究已经从基本机制转向临床转化。结论：BaP可能通过靶向TP53驱动GBM，为GBM的预防和治疗提供新的思路。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Deciphering the carcinogenic role of benzo[a]pyrene in glioblastoma: Insights from network toxicology, single-cell transcriptomics, and Mendelian randomization

Background

Benzo[a]pyrene (BaP) is a known environmental carcinogen linked to multiple tumors, but its role in glioblastoma (GBM) remains poorly understood. This study aimed to explore BaP’s tumorigenic mechanisms in GBM through an integrated approach combining network toxicology, single-cell transcriptomics, Mendelian randomization, and bibliometric analysis.

Methods

BaP target genes were predicted using ChEMBL, SEA, and PharmMapper, and GBM-related genes were retrieved from GeneCards, OMIM, and TTD. Overlapping genes were used to construct a protein–protein interaction network in Cytoscape. Molecular docking and molecular dynamics simulations were performed to assess BaP–target interactions. Single-cell RNA-seq data (GSE131928) were analyzed to profile gene expression in GBM subpopulations. Mendelian randomization assessed causal relationships between core genes and GBM risk, and findings were validated in vitro. Bibliometric analysis tracked research trends on these genes.

Results

31 overlapping genes were identified. TP53 was highly expressed in MES-like and AC-like malignant cells as well as CD8⁺ Tex cells. MR revealed a significant inverse association between TP53 expression and GBM risk (OR = 0.13, 95 % CI: 0.04–0.47, p = 0.002). Docking and simulation showed strong BaP–TP53 binding, confirmed by in vitro experiments. Bibliometrics indicated that TP53 research in GBM has shifted from basic mechanisms to clinical translation.

Conclusion

BaP may drive GBM by targeting TP53, offering insights for GBM prevention and therapy.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

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.