GNG12 overexpression inhibits triple-negative breast cancer cell proliferation, migration, and invasion.

Guanine nucleotide-binding protein subunit gamma-12 (GNG12), a G protein γ-subunit, has been identified as a potential regulator of tumor biology. However, its functional relevance in triple-negative breast cancer (TNBC) remains unclear. In this study, we integrated pan-cancer transcriptomic analyses with experimental validation in TNBC models to investigate the expression patterns, clinicopathological significance, and biological roles of GNG12. GNG12 was found to be broadly downregulated across diverse cancer types, and its reduced expression was significantly associated with unfavorable patient survival outcomes. Low GNG12 expression correlated with adverse clinicopathological features in breast cancer (BRCA). Moreover, it was associated with poorer outcomes in TNBC patient cohorts. Functional assays demonstrated that GNG12 overexpression inhibited TNBC cell proliferation, migration, and invasion, whereas GNG12 knockdown exerted the opposite effects. Pathway analysis and western blotting indicated that GNG12 expression was associated with altered PI3K/AKT pathway activity. Additionally, mutations at S2 and S33-both located within predicted phosphorylation sites-were identified as candidate regulatory alterations whose functional relevance requires further validation. Moreover, GNG12 expression was positively correlated with RNA methylation-related markers and inversely associated with promoter methylation. Taken together, GNG12 was downregulated in TNBC and associated with suppression of malignant cellular phenotypes; however, its clinical significance and mechanistic relationship with PI3K/AKT signaling require further validation in larger cohorts and additional experimental models.