Targeting GRIA3 in Breast Cancer: Cuproptosis-Related Genes Unveil Immune Dysregulation and Prognostic Stratification.

Breast cancer (BRCA) is a major global health challenge. This study is aimed to discover the cuproptosis-related genes and their roles in BRCA treatment. Bioinformatic analyses, including clinicopathological, enrichment, and protein interaction studies, were performed. A predictive risk model was established and consensus clustering was conducted to detect new molecular subtypes. The tumor immune microenvironment (TIME) and immune status of the identified subgroups were assessed. GRIA3 was knocked down by shRNA, and CCK-8, EdU, wound healing, and Transwell assays were used to assess changes in cell viability, proliferation, migration, and invasion. CD8+ T cell migration was analyzed using Transwell assays, and the expression levels of IFN-γ and TNF-α were monitored via ELISA. Cuproptosis-related genes in BRCA patients were characterized. An immune prognostic model (IPM) predicted high-risk patients. Key markers (FABP7, PLA2G2D, RDH16, etc.) were linked to BRCA stages. TIME analysis revealed higher immune checkpoint expression (CD274, CTLA-4, etc.) in low-risk groups. The GRIA3 gene was shown to be highly expressed in BRCA cells, promoting cell proliferation, migration and invasion. Conversely, knockdown of GRIA3 attenuated these oncogenic properties and, importantly, enhanced the migration and effector cytokine (IFN-γ, TNF-α) secretion of co-cultured CD8+ T cells. The expression of cuproptosis-related genes is correlated with the immune microenvironment of BRCA patients and could serve as a predictive marker for prognosis as well as a target for treatment. GRIA3 exhibits pro-tumor activity in BRCA cells and may represent a potential therapeutic target.