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

IF 2.7 4区 医学 Q3 TOXICOLOGY
Chenyu Liang, Weicheng Tian, Hengxi Zeng, Ziyang Xia, Zijie Luo, Yue Zhuo, Minlian Pan, Kangbu Wu, Siyu Xiong, Xuejing Lin, Xinchun Li, Jiaxi Yu
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引用次数: 0

摘要

邻苯二甲酸一(2-乙基己基)酯(MEHP)是一种普遍存在的环境污染物和内分泌干扰化学物质(EDC),被确定为潜在的致癌物。新兴研究已经开始阐明MEHP对前列腺癌(PCa)的影响,但其致病作用和潜在的分子机制尚不清楚。本研究旨在探讨MEHP影响PCa发生和发展的分子基础。利用网络毒理学和生物信息学技术,我们在PCa中鉴定了mehp相关的致病基因。采用多种机器学习集成算法建立了一种创新的预测模型,并使用受试者工作特征(ROC)曲线下面积对其性能进行了验证。此外,在单细胞分辨率下,鉴定了关键的mehp相关分子,包括几个关键基因,在PCa的致癌进展中的作用。通过构建环境污染物-关键基因- pca网络,研究了环境污染物与关键基因VGF、ASPN、FOXS1、APLN和AMH之间的相互作用。分子对接研究表明,APLN、FOXS1和ASPN基因对MEHP具有良好的结合能和高亲和力。本研究结果为了解MEHP在PCa中的致病作用及其潜在的分子机制提供了理论基础。推动网络毒理学、分子对接、机器学习、单细胞分析等在环境污染物研究中的应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.

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来源期刊
CiteScore
7.00
自引率
6.10%
发文量
145
审稿时长
1 months
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.
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