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  3. Revealing the role of bisphenol A on prostate cancer progression and identifying potential targets: A comprehensive analysis from population cohort to molecular mechanism

Revealing the role of bisphenol A on prostate cancer progression and identifying potential targets: A comprehensive analysis from population cohort to molecular mechanism

  • Ecotoxicol Environ Saf. 2025 May:296:118209. doi: 10.1016/j.ecoenv.2025.118209.
Xianghong Zhou 1,  Chuzhong Wei 1,  Xing Liu 2,  Zilong Zhang 1,  Yuwei Wu 1,  Bin Zeng 1,  Yumin Jin 1,  Yixiao Shi 1,  Zengnan Mo 3,  Jiwen Cheng 3,  Xiaoli Zou 4,  Qiang Wei 1,  Lu Yang 5,  Shi Qiu 6
Affiliations

Affiliations

  • 1 Department of Urology and Institute of Urology and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China.
  • 2 Department of Urology and Institute of Urology and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China; The First People's Hospital of Mianyang, Mianyang, Sichuan Province 621000, China.
  • 3 Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi 530021, China; Guangxi collaborative innovation center for genomic and personalized medicine, Guangxi key laboratory for genomic and personalized medicine, Guangxi key laboratory of colleges and universities, Nanning, Guangxi 530021, China; Department of Urology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
  • 4 Department of Sanitary Technology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
  • 5 Department of Urology and Institute of Urology and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: wycleflue@163.com.
  • 6 Department of Urology and Institute of Urology and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: qiushi@scu.edu.cn.
PMID: 40249974 DOI: 10.1016/j.ecoenv.2025.118209
Abstract

Bisphenol A (BPA) is a widespread environmental pollutant whose exact effects on prostate Cancer (PCa) progression remain understudied. This study aims to investigate the effect and underlying molecular mechanisms between BPA exposure and PCa in a comprehensive approach. The multicenter cohort study found that BPA exposure plays an important role in promoting biochemical recurrence and death of PCa. BPA exposure significantly promoted PCa progression in both the animal model and in vitro experiments. RNA Sequencing revealed a disruption of mitochondrial energy homeostasis in BPA-treated cells. In multiple datasets, 17 prognostic genes such as PFKFB4 were obtained to construct and verify a mitochondrial energy metabolism Score system. Based on network toxicology methods and transcriptome Sequencing data, ESR1 was identified as a potential transcription factor targeting glycolytic enzyme PFKFB4 under BPA exposure. With the support of lncRNA and circRNA Sequencing data, a molecular regulatory network of BPA promoting prostate Cancer through mitochondrial energy metabolism reprogramming was constructed. Further molecular docking revealed that BPA has higher binding free energy to ERα than its natural ligand estradiol. Given the widespread presence of BPA in the environment, minimizing exposure to this chemical could represent a feasible approach in improving clinical outcomes.

Keywords

Bisphenol A; Malignant Progression; Mitochondrial Energy Metabolism; Multicenter Cohort; Prostate Cancer.

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