Bisphenol A promotes OSCC progression via GABBR1-mediated MAPK signaling and macrophage polarization: A network toxicology based study

作者：Qi He, Anquan Ma, Ziqing Yang, Xinyu Pang, Chen Li, Jiayong Diao, Yuxuan Liu, Quanzhen Liu, Qingyue Zhang, Zuoqing Dong, Dongjiao Zhang · 发表于：Ecotoxicology and Environmental Safety · 年份：2025 · DOI：10.1016/j.ecoenv.2025.118835 · 被引用次数：6 · 研究领域：Effects and risks of endocrine disrupting chemicals、Cancer Cells and Metastasis、Microplastics and Plastic Pollution

BACKGROUND: Bisphenol A (BPA), an environmental pollutant, has been implicated in oral squamous cell carcinoma (OSCC) progression, yet its molecular mechanisms remain unclear. This study explores the role of GABBR1 in BPA-induced OSCC malignancy. METHODS: Bioinformatics analysis identified GABBR1 as a key gene in OSCC. Expression patterns and clinical relevance were assessed using TCGA, GTEx, and HPA databases. Molecular docking and dynamics simulations further elucidated the binding interaction between BPA and GABBR1. Functional assays, including western blot, immunofluorescence, CCK-8, EdU, and transwell evaluated the effects of BPA exposure and GABBR1 knockdown on OSCC cell function. Transwell co-culture, RT-PCR and ELISA assays examined exosome-mediated interactions between OSCC cells and macrophages. RESULTS: BPA exposure enhanced OSCC proliferation, migration, and invasion while promoting stemness through the GABBR1/MEK/ERK signaling pathway. Additionally, it induced M2 macrophage polarization via exosomal communication, contributing to an immunosuppressive microenvironment. CONCLUSION: This study uncovers a novel mechanism by which BPA promotes OSCC progression via GABBR1-mediated signaling and exosome-driven immunomodulation, highlighting GABBR1 as a potential therapeutic target in BPA-associated OSCC.