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揭开PFOA与膀癌之间的联系:一项综合网络毒理学,分子对接和实验验证的研究

Huaqing Yan¹, Chunyan Yin¹, Fan Xu¹

¹Department of Urology, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang 315000, PR China.

Toxicology and applied pharmacology

|March 7, 2026

概括

暴露在 perfluorooctanoic 酸 (PFOA) 中可以通过调节 NUDT1 的基因来促进膀癌,NUDT1 是一种增强癌细胞生长和迁移的基因. NUDT1可以作为PFOA诱导的膀癌的生物标志物和治疗标.

科学领域:

环境毒理学环境毒理学
分子瘤学分子瘤学
生物信息学是一种生物信息学.

背景情况:

perfluorooctanoic 酸 (PFOA) 是一种环境污染物,与膀癌风险增加有关.
导致PFOA在膀癌中的致癌作用的精确分子机制尚不完全理解.

研究的目的:

阐明通过PFOA促进膀癌症发展的分子途径.
为了确定潜在的分子生物标志物和PFOA相关的膀癌的治疗点.

主要方法:

转录组数据与网络毒理学和机器学习方法的整合.
在PFOA暴露和膀癌数据集之间识别共享基因.
基于机器学习的预后基因签名的开发.
分子对接模拟用于预测PFOA基因相互作用.
在体外功能实验 (细胞增殖,迁移试验) 和基因淘汰研究.

主要成果:

总共确定了125个与PFOA暴露和膀癌相关的共享基因.
使用机器学习开发了一种16基因的预后特征.
NUDT1被确定为具有高PFOA结合亲和度的顶级候选基因.
暴露于PFOA导致NUDT1的表达增加,促进膀癌细胞的增殖和迁移.
NUDT1 knockdown逆转了PFOA诱导的恶性表型,并部分减轻了PFOA的影响.

结论:

通过对NUDT1.1的上调调节,PFOA促进了膀癌的进展.
NUDT1在调解PFOA在膀癌中的致癌作用方面发挥着关键作用.
NUDT1代表了与PFOA相关的膀癌的潜在诊断生物标志物和治疗点.

关键词:

膀癌是一种癌症.这就是PFOA的PFOA.预测预后预测预测幸存的生存方式

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