Gamma-aminobutyric acid transaminase mediates tumor suppression in renal cell carcinoma through the cGAS-STING-interferon-β axis.

Clear cell renal cell carcinoma (ccRCC) is resistant to conventional radiotherapy and chemotherapy, creating an urgent need for novel therapeutic strategies. Although GABA transaminase (ABAT) is involved in metabolic reprogramming as reported, its precise function and molecular mechanisms in ccRCC remain unclear. Here, we demonstrate that ABAT overexpression suppresses tumor growth both in vitro and in vivo. Mechanistically, ABAT mediates the cGAS-STING signaling pathway, and interacts with protein arginine methyltransferase 5 (PRMT5), thereby enhances interferon signaling. Besides, ABAT was found to reduce the infiltration of regulatory T cells within the tumor microenvironment. Collectively, these results suggest that ABAT represents a potential therapeutic target in clear cell renal cell carcinoma.