To characterize the expression of G12 subfamily members (GNA13 and GNA12) in oral squamous cell carcinoma (OSCC) and to evaluate their functional roles in regulating OSCC cell proliferation, migration and invasion.

Public bioinformatic resources were interrogated to profile GNA12 and GNA13 expression and associated functional pathways. Immunohistochemistry was performed on 102 OSCC and 48 adjacent non‑neoplastic tissue specimens, with correlation analyses against clinicopathological parameters and patient survival. Protein and transcript levels were validated in OSCC cell lines by Western blotting and RT‑qPCR. Loss‑of‑function studies using siRNA were followed by CCK‑8, colony formation, Transwell migration/invasion and wound‑healing assays to assess cellular phenotypes.

Bioinformatic analyses showed significant upregulation of GNA13 and GNA12 in OSCC ( P < 0.001) and enrichment of Rho-mediated signalling pathways. Immunohistochemistry confirmed increased GNA13 and GNA12 expression in tumour tissues compared with adjacent mucosa ( P < 0.05). GNA13 expression correlated with tumour differentiation ( P = 0.013) and nodal metastasis ( P = 0.033), whereas GNA12 expression correlated with tumour differentiation ( P = 0.010) and clinical stage ( P = 0.027). Overexpression of both genes was associated with poorer overall survival ( P < 0.001). Elevated expression in OSCC cell lines was validated by Western blot and RT-qPCR. Functional assays demonstrated that siRNA-mediated knockdown of GNA13 or GNA12 significantly reduced cell viability, colony formation, migration and invasion compared with controls ( P < 0.05).

Elevated expressions of GNA13 and GNA12 in OSCC tumor tissues and cells are associated with poor patient prognosis. Targeted knockout of GNA13 and GNA12 effectively suppresses malignant behaviors of OSCC, including cell proliferation, migration abilities, and invasive potential. The G12 subfamily may represent a novel therapeutic target for OSCC treatment.