Abstract
B-cell translocation gene 3 (BTG3), a tumor suppressor, is reduced in expression in several malignancies, including ovarian cancer, colorectal cancer, and gastric cancer, but its role in oral squamous cell carcinoma (OSCC) is unknown. This study aimed to investigate the expression of BTG3 in OSCC, as well as explore its impact on the biological behavior of OSCC and the potential regulatory mechanisms. BTG3 expression levels in OSCC and normal tissues were examined using the GEO database and the Kaplan-Meier Plotter database was used for survival analysis. Western blotting and quantitative real-time PCR were used to assess BTG3 expression levels in OSCC tissues and neighboring normal tissues, as well as in oral epithelial cells (HOEC) and OSCC cell lines (CAL27 and SCC15). We found the expression level of BTG3 was lower in OSCC tissues than in surrounding normal tissues, with higher expression indicating a better prognosis. In vitro assay demonstrated that overexpression of BTG3 inhibited OSCC cell proliferation, migration, and invasion, resulting in cell cycle arrest at the G1 phase, as well as negatively regulating the PI3K/AKT signaling pathway and inhibiting EMT progression; knockdown had the opposite effect. BTG3 represents a potential therapeutic target in OSCC treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-37518-7.