Abstract
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.
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Data availability
The datasets generated and analysed during the current study are available in the NCBI Sequence Read Archive (SRR36638439, SRR36638436, SRR36638441, SRR36638438, SRR36638440, SRR36638437).
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Funding
This study received financial support from the Ministry of Science and Technology of the People’s Republic of China (Hongzhao Li, 2022YFC3602901).
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Yi Feng was responsible for conceptualization, data curation, formal analysis, investigation, methodology, and writing of the original draft. Senming Cao was responsible for investigation and methodology. Tianwei Cai was responsible for formal analysis, validation, and methodology. Yin Lu was responsible for formal analysis and investigation. Bin Jiang was responsible for formal analysis and investigation. Zexuan Lv was responsible for formal analysis and investigation. Jinlu Tang was responsible for investigation. Chunyu Liu was responsible for investigation. Qi Wang was responsible for formal analysis. Ji Feng was responsible for investigation. Zheng Wang was responsible for resources. Qi Ai was responsible for resources. Xupeng Zhao was responsible for resources. KL was responsible for conceptualization and data curation. Qiang Cheng was responsible for conceptualization, data curation, and funding acquisition. Wenmei Fan was responsible for conceptualization, resources, supervision, and funding acquisition. Hongzhao Li was responsible for conceptualization, resources, data curation, formal analysis, supervision, funding acquisition, and writing of the original draft.
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Renal tissue samples were acquired from the Kidney Biobank of the Department of Urology at the Chinese PLA General Hospital during the period spanning January to December 2019. The study protocol involving human specimens received ethical approval from the Chinese PLA General Hospital Ethics Committee (Approval No. S2013-065-01). Confirming The study is reported in accordance with ARRIVE guidelines. All methods were carried out in accordance with relevant guidelines and regulations.
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Feng, Y., Cao, S., Cai, T. et al. Gamma-aminobutyric acid transaminase mediates tumor suppression in renal cell carcinoma through the cGAS-STING–interferon-β axis. Sci Rep (2026). https://doi.org/10.1038/s41598-026-42861-w
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DOI: https://doi.org/10.1038/s41598-026-42861-w
