The ubiquitin-specific protease USP2a enhances tumor progression by targeting cyclin A1 in bladder cancer

Jayoung Kim1, Wun-Jae Kim, Zhiqian Liu

  • 1Division of Cancer Biology and Therapeutics, Departments of Surgery and Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Jayoung.Kim@cshs.org

Insights

The deubiquitinating enzyme USP2a promotes bladder cancer growth and chemoresistance by stabilizing cyclin A1. Targeting USP2a may offer a new therapeutic strategy for bladder tumors, potentially combined with chemotherapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The deubiquitinating enzyme USP2a exhibits oncogenic properties in various cancers.
  • USP2a dysregulation is linked to tumor progression, especially in prostate cancer.
  • The specific role and mechanism of USP2a in bladder cancer remain largely unexplored.

Purpose of the Study:

  • To investigate the role of USP2a as an oncoprotein in bladder cancer.
  • To elucidate the underlying molecular mechanism of USP2a action in bladder cancer cells.

Main Methods:

  • Enforced expression and loss of USP2a in bladder cancer cells.
  • Assessment of proliferation, invasion, and migration.
  • Chemosensitivity assays.
  • Analysis of USP2a interaction with cyclin A1 and its ubiquitination status.

Main Results:

  • USP2a overexpression enhanced bladder cancer cell proliferation, invasion, migration, and chemoresistance.
  • USP2a depletion reduced these aggressive phenotypes and increased chemosensitivity.
  • USP2a stabilized cyclin A1 by inhibiting its ubiquitination and degradation, leading to increased proliferation.

Conclusions:

  • USP2a functions as an oncoprotein in bladder cancer.
  • USP2a promotes bladder cancer progression by stabilizing cyclin A1.
  • Targeting USP2a presents a potential therapeutic strategy for bladder cancer, possibly in combination with chemotherapy.

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