{"title":"基于网络毒理学和分子对接方法揭示邻苯二甲酸单(2-乙基己基)酯对前列腺癌的影响","authors":"Chenyu Liang, Weicheng Tian, Hengxi Zeng, Ziyang Xia, Zijie Luo, Yue Zhuo, Minlian Pan, Kangbu Wu, Siyu Xiong, Xuejing Lin, Xinchun Li, Jiaxi Yu","doi":"10.1002/jat.4826","DOIUrl":null,"url":null,"abstract":"<p><p>Mono(2-ethylhexyl) phthalate (MEHP) is a ubiquitous environmental contaminant and endocrine-disrupting chemical (EDC), identified as a potential carcinogen. Emerging studies have begun to elucidate the impact of MEHP on prostate cancer (PCa), yet its pathogenic effects and the underlying molecular mechanisms remain unclear. This study seeks to explore the molecular basis through which MEHP affects the onset and progression of PCa. Using network toxicology and bioinformatics, we identified MEHP-related pathogenic genes in PCa. An innovative predictive model was developed by employing multiple machine learning ensemble algorithms, and its performance was validated using the area under the receiver operating characteristic (ROC) curve. Furthermore, at the single-cell resolution, the role of key MEHP-associated molecules, including several critical genes, in the oncogenic progression of PCa was identified. Through the construction of an environmental pollutant-key gene-PCa network, we investigated the interactions between environmental pollutants and the key genes VGF, ASPN, FOXS1, APLN, and AMH. Molecular docking studies demonstrated that the APLN, FOXS1, and ASPN genes exhibited favorable binding energies and high affinities for MEHP. The findings of this study provide a theoretical foundation for understanding the pathogenic role of MEHP in PCa and its potential molecular mechanisms. They also promote the application of network toxicology, molecular docking, machine learning, and single-cell analysis in the study of environmental pollutants.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7000,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Revealing the Impact of Mono(2-ethylhexyl) Phthalate (MEHP) on Prostate Cancer Based on Network Toxicology and Molecular Docking Approaches.\",\"authors\":\"Chenyu Liang, Weicheng Tian, Hengxi Zeng, Ziyang Xia, Zijie Luo, Yue Zhuo, Minlian Pan, Kangbu Wu, Siyu Xiong, Xuejing Lin, Xinchun Li, Jiaxi Yu\",\"doi\":\"10.1002/jat.4826\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Mono(2-ethylhexyl) phthalate (MEHP) is a ubiquitous environmental contaminant and endocrine-disrupting chemical (EDC), identified as a potential carcinogen. Emerging studies have begun to elucidate the impact of MEHP on prostate cancer (PCa), yet its pathogenic effects and the underlying molecular mechanisms remain unclear. This study seeks to explore the molecular basis through which MEHP affects the onset and progression of PCa. Using network toxicology and bioinformatics, we identified MEHP-related pathogenic genes in PCa. An innovative predictive model was developed by employing multiple machine learning ensemble algorithms, and its performance was validated using the area under the receiver operating characteristic (ROC) curve. Furthermore, at the single-cell resolution, the role of key MEHP-associated molecules, including several critical genes, in the oncogenic progression of PCa was identified. Through the construction of an environmental pollutant-key gene-PCa network, we investigated the interactions between environmental pollutants and the key genes VGF, ASPN, FOXS1, APLN, and AMH. Molecular docking studies demonstrated that the APLN, FOXS1, and ASPN genes exhibited favorable binding energies and high affinities for MEHP. The findings of this study provide a theoretical foundation for understanding the pathogenic role of MEHP in PCa and its potential molecular mechanisms. They also promote the application of network toxicology, molecular docking, machine learning, and single-cell analysis in the study of environmental pollutants.</p>\",\"PeriodicalId\":15242,\"journal\":{\"name\":\"Journal of Applied Toxicology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2025-06-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Applied Toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/jat.4826\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"TOXICOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Applied Toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/jat.4826","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"TOXICOLOGY","Score":null,"Total":0}
Revealing the Impact of Mono(2-ethylhexyl) Phthalate (MEHP) on Prostate Cancer Based on Network Toxicology and Molecular Docking Approaches.
Mono(2-ethylhexyl) phthalate (MEHP) is a ubiquitous environmental contaminant and endocrine-disrupting chemical (EDC), identified as a potential carcinogen. Emerging studies have begun to elucidate the impact of MEHP on prostate cancer (PCa), yet its pathogenic effects and the underlying molecular mechanisms remain unclear. This study seeks to explore the molecular basis through which MEHP affects the onset and progression of PCa. Using network toxicology and bioinformatics, we identified MEHP-related pathogenic genes in PCa. An innovative predictive model was developed by employing multiple machine learning ensemble algorithms, and its performance was validated using the area under the receiver operating characteristic (ROC) curve. Furthermore, at the single-cell resolution, the role of key MEHP-associated molecules, including several critical genes, in the oncogenic progression of PCa was identified. Through the construction of an environmental pollutant-key gene-PCa network, we investigated the interactions between environmental pollutants and the key genes VGF, ASPN, FOXS1, APLN, and AMH. Molecular docking studies demonstrated that the APLN, FOXS1, and ASPN genes exhibited favorable binding energies and high affinities for MEHP. The findings of this study provide a theoretical foundation for understanding the pathogenic role of MEHP in PCa and its potential molecular mechanisms. They also promote the application of network toxicology, molecular docking, machine learning, and single-cell analysis in the study of environmental pollutants.
期刊介绍:
Journal of Applied Toxicology publishes peer-reviewed original reviews and hypothesis-driven research articles on mechanistic, fundamental and applied research relating to the toxicity of drugs and chemicals at the molecular, cellular, tissue, target organ and whole body level in vivo (by all relevant routes of exposure) and in vitro / ex vivo. All aspects of toxicology are covered (including but not limited to nanotoxicology, genomics and proteomics, teratogenesis, carcinogenesis, mutagenesis, reproductive and endocrine toxicology, toxicopathology, target organ toxicity, systems toxicity (eg immunotoxicity), neurobehavioral toxicology, mechanistic studies, biochemical and molecular toxicology, novel biomarkers, pharmacokinetics/PBPK, risk assessment and environmental health studies) and emphasis is given to papers of clear application to human health, and/or advance mechanistic understanding and/or provide significant contributions and impact to their field.