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Published on: June 23, 2013
Bisphenol A promotes OSCC progression via GABBR1-mediated MAPK signaling and macrophage polarization: A network
Qixuan He1, Anquan Ma1, Ziqing Yang1
1Department of Implantology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No.44-1 Wenhua Road West, 250012, Jinan, Shandong, China.
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.
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