Exploring the toxicological mechanisms of atrazine in prostate cancer by network toxicology and molecular docking

IF 2.8 4区 医学 Q2 REPRODUCTIVE BIOLOGY
Jinwen Mi , Siyuan Wang, Yifan Hong, Shengde Wu, Guanghui Wei
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Abstract

Atrazine (ATZ) is the second most used herbicide against broadleaf and grassy weeds worldwide. ATZ persists in soil and water due to its long half-life, and is considered an endocrine disrupting chemical for humans. Epidemiological studies have indicated an intimate relationship between ATZ and the pathogenesis of prostate cancer (PCa). However, the underlying toxicological mechanisms remain barely elucidated. Leveraging the CTD, GeneCards, OMIM, PharmGKB, and TTD databases, we identified 154 target genes associated with ATZ exposure and PCa. Using STRING and Cytoscape tools, a PPI network was constructed, and five key genes involved in ATZ-induced PCa toxicity including TP53, JUN, AKT1, BCL2, and IL1B were extracted. Enrichment analysis of target genes highlighted the association of ATZ with pathways integral to PCa development. Expression analysis, ROC curve analysis, immune correlation analysis, and single-gene GSEA of these key genes confirmed their pivotal role in PCa biology. Furthermore, we employed Autodock Vina for molecular docking analysis, demonstrating strong binding between ATZ and the key genes. Collectively, our findings suggest that ATZ may serve as a potential environmental pollutant influencing the pathogenesis of PCa through interactions with key proteins and signaling pathways, offering a theoretical groundwork for the comprehensive prevention and medical management of PCa patients.
通过网络毒理学和分子对接探讨阿特拉津在前列腺癌中的毒理学机制
莠去津(atzine, ATZ)是世界上第二大用于防治阔叶草杂草的除草剂。由于半衰期长,ATZ在土壤和水中持续存在,被认为是一种干扰人类内分泌的化学物质。流行病学研究表明,ATZ与前列腺癌(PCa)的发病机制密切相关。然而,潜在的毒理学机制仍然几乎没有阐明。利用CTD、GeneCards、OMIM、PharmGKB和TTD数据库,我们确定了154个与ATZ暴露和PCa相关的靶基因。利用STRING和Cytoscape工具构建PPI网络,提取atz诱导PCa毒性的5个关键基因,包括TP53、JUN、AKT1、BCL2和IL1B。靶基因的富集分析强调了ATZ与PCa发展过程中不可或缺的途径的关联。这些关键基因的表达分析、ROC曲线分析、免疫相关性分析和单基因GSEA分析证实了它们在PCa生物学中的关键作用。此外,我们使用Autodock Vina进行分子对接分析,证明了ATZ与关键基因之间的强结合。综上所述,我们的研究结果表明,ATZ可能是一种潜在的环境污染物,通过与关键蛋白和信号通路的相互作用影响PCa的发病机制,为PCa患者的综合预防和医疗管理提供理论基础。
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来源期刊
Reproductive toxicology
Reproductive toxicology 生物-毒理学
CiteScore
6.50
自引率
3.00%
发文量
131
审稿时长
45 days
期刊介绍: Drawing from a large number of disciplines, Reproductive Toxicology publishes timely, original research on the influence of chemical and physical agents on reproduction. Written by and for obstetricians, pediatricians, embryologists, teratologists, geneticists, toxicologists, andrologists, and others interested in detecting potential reproductive hazards, the journal is a forum for communication among researchers and practitioners. Articles focus on the application of in vitro, animal and clinical research to the practice of clinical medicine. All aspects of reproduction are within the scope of Reproductive Toxicology, including the formation and maturation of male and female gametes, sexual function, the events surrounding the fusion of gametes and the development of the fertilized ovum, nourishment and transport of the conceptus within the genital tract, implantation, embryogenesis, intrauterine growth, placentation and placental function, parturition, lactation and neonatal survival. Adverse reproductive effects in males will be considered as significant as adverse effects occurring in females. To provide a balanced presentation of approaches, equal emphasis will be given to clinical and animal or in vitro work. Typical end points that will be studied by contributors include infertility, sexual dysfunction, spontaneous abortion, malformations, abnormal histogenesis, stillbirth, intrauterine growth retardation, prematurity, behavioral abnormalities, and perinatal mortality.
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