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

  • Sci Rep. 2026 Mar 11;16(1):13082. doi: 10.1038/s41598-026-42861-w.
Yi Feng  #  1  2  3 ,  Senming Cao  #  1  2  4 ,  Tianwei Cai  #  1  2  3 ,  Yin Lu  1  4 ,  Bin Jiang  1  3 ,  Zexuan Lv  1  4 ,  Jinlu Tang  1  3 ,  Fan Gao  1  2  4 ,  Xupeng Zhao  1 ,  Chunyu Liu  1  2  3 ,  Qi Wang  1  2  3 ,  Ji Feng  1  2  3 ,  Zheng Wang  1  2  3 ,  Qing Ai  1 ,  Qiang Cheng  5  6 ,  Wenmei Fan  7  8 ,  Hongzhao Li  9
Affiliations
  • 1. Department of Urology, The Third Medical Center of PLA General Hospital, Beijing, China.
  • 2. Department of Urology Laboratory, Chinese PLA General Hospital, Beijing, China.
  • 3. Medical School of PLA, Beijing, China.
  • 4. Medical School of NanKai University, TianJing, China.
  • 5. Department of Urology, The Third Medical Center of PLA General Hospital, Beijing, China. [email protected].
  • 6. Department of Urology Laboratory, Chinese PLA General Hospital, Beijing, China. [email protected].
  • 7. Department of Urology, The Third Medical Center of PLA General Hospital, Beijing, China. [email protected].
  • 8. Department of Urology Laboratory, Chinese PLA General Hospital, Beijing, China. [email protected].
  • 9. Department of Urology, The Third Medical Center of PLA General Hospital, Beijing, China. [email protected].
  • # Contributed equally.
PMID: 41813748 DOI: 10.1038/s41598-026-42861-w
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.

Keywords
Gamma-aminobutyric acid transaminase; IFN-β; PRMT5; cGAS-STING; ccRCC.
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