O-GlcNAcylation of KAT2A Enhances Bladder Cancer Proliferation by Inhibiting the KAT2A-TRIM22 Interaction

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Wenjie Yang1, Zhaoheng Jin1, Ziyi Li1

  • 1Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Cancer Science
|May 11, 2026
PubMed

Insights

O-GlcNAcylation stabilizes Lysine acetyltransferase 2A (KAT2A) in bladder cancer (BLCA) by preventing its degradation. This post-translational modification promotes tumor growth by upregulating oncogenes, suggesting KAT2A O-GlcNAcylation as a therapeutic target for BLCA.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Lysine acetyltransferase 2A (KAT2A) is a Histone Acetyltransferase (HAT) involved in cancer, but its role in bladder cancer (BLCA) is unclear.
  • Post-translational modifications (PTMs), like O-GlcNAcylation, are critical in cancer development and progression.

Purpose of the Study:

  • To investigate the impact of O-GlcNAcylation on KAT2A stability and its oncogenic role in BLCA.
  • To elucidate the molecular mechanisms underlying KAT2A O-GlcNAcylation in bladder cancer.

Main Methods:

  • Quantitative real-time PCR (qPCR) and immunohistochemistry on 96 paired BLCA and normal tissues.
  • Functional assays including siRNA knockdown, co-immunoprecipitation (co-IP), ubiquitination, and chromatin immunoprecipitation (ChIP) in BLCA cell lines and xenograft models.

Main Results:

  • KAT2A expression is significantly elevated in BLCA tissues.
  • O-GlcNAcylation at serine 583 (S583) stabilizes KAT2A by inhibiting TRIM22-mediated ubiquitination.
  • Hyper-O-GlcNAcylation enhances H3K9 acetylation and upregulates oncogenes (TGFB1, E2F1, GPX4), promoting tumor cell proliferation and growth. S583 mutation destabilizes KAT2A and suppresses oncogene expression.

Conclusions:

  • KAT2A plays a critical role in BLCA progression.
  • O-GlcNAcylation at S583 is a key regulatory mechanism for KAT2A stability and oncogenic function in BLCA.
  • Targeting KAT2A O-GlcNAcylation presents a potential therapeutic strategy for bladder cancer.
Keywords:
KAT2AO‐GlcNAcylationbladder cancerproliferationubiquitination

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