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Updated: May 10, 2025

Mouse Bladder Wall Injection
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Non-classic deubiquitinase USP13 inhibits bladder cancer metastasis through destabilizing cytoplasmic KDM3A

Hongji Hu1,2, Xiangpeng Zhan1,2, Yunqiang Xiong1,2

  • 1Department of Urology, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.

Oncogene
|April 19, 2025
PubMed

Insights

High KDM3A levels drive bladder cancer progression and metastasis. The protein USP13 degrades KDM3A, inhibiting tumor growth and spread, suggesting USP13 as a therapeutic target for bladder cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Bladder cancer (BLCa) metastasis is a major cause of patient mortality.
  • The role of histone demethylase KDM3A in bladder cancer progression remains unclear.
  • KDM3A regulates gene transcription by removing H3K9 methylation marks.

Purpose of the Study:

  • To investigate the role of KDM3A in bladder cancer growth and metastasis.
  • To elucidate the molecular mechanisms underlying KDM3A's function in bladder cancer.
  • To identify potential therapeutic targets for bladder cancer treatment.

Main Methods:

  • KDM3A expression analysis in bladder cancer tissues.
  • In vitro and in vivo assays to assess the effects of KDM3A silencing on bladder cancer cells.
  • Investigation of the interaction between USP13 and KDM3A.
  • Ubiquitination and proteasomal degradation assays.
  • Bladder cancer liver metastasis xenograft model.

Main Results:

  • High KDM3A expression correlates with advanced bladder cancer.
  • KDM3A silencing suppresses bladder cancer cell proliferation, migration, and invasion.
  • USP13 interacts with KDM3A, promoting its cytoplasmic degradation via the proteasome.
  • USP13 is downregulated in bladder cancer tissues and inversely correlated with KDM3A levels.
  • USP13 inhibits bladder cancer metastasis by destabilizing KDM3A.

Conclusions:

  • KDM3A is a key driver of bladder cancer growth and metastasis.
  • USP13 acts as a tumor suppressor by degrading KDM3A.
  • Targeting the USP13/KDM3A complex offers a potential therapeutic strategy for bladder cancer.

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