OTUD4 Inhibits Prostate Cancer by Deubiquitinating MYH9

Zheng Qin1,2, Yueyao Zhang3, Dongze Liu4

  • 1Tianjin Key Laboratory of Precision Medicine for Sex Hormones and Diseases, The Second Hospital of Tianjin Medical University, Tianjin, 300211, China.

Oncology Research
|April 3, 2026
PubMed
Abstract

Insights

Ovarian tumor family deubiquitinase 4 (OTUD4) acts as a tumor suppressor in prostate cancer by preventing myosin-9 (MYH9) degradation. This discovery offers new therapeutic targets for improving prostate cancer prognosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Prostate cancer is a leading cause of cancer death in men, necessitating novel therapeutic targets.
  • The role of Ovarian Tumor Family Deubiquitinase 4 (OTUD4) in prostate cancer pathogenesis is currently unknown.
  • Identifying new biological targets is critical for improving patient outcomes.

Purpose of the Study:

  • To investigate OTUD4 as a potential therapeutic target and diagnostic marker in prostate cancer.
  • To elucidate the underlying mechanisms of OTUD4's function in prostate cancer.

Main Methods:

  • Utilized cell culture, CCK-8, colony formation, Transwell, and EdU assays for in vitro analysis.
  • Employed immunofluorescence, Western blot, qRT-PCR, and protein mass spectrometry for molecular investigations.
  • Validated findings in vivo using nude mouse xenograft models and IHC/H&E staining.

Main Results:

  • OTUD4 expression was found to be downregulated in prostate cancer tissues and correlated with poorer prognosis.
  • OTUD4 was identified to directly inhibit the degradation of myosin-9 (MYH9) protein through deubiquitination.
  • Overexpression of MYH9 suppressed prostate cancer growth, suggesting a tumor-suppressive role mediated by cell adhesion molecules.

Conclusions:

  • OTUD4 functions as a tumor suppressor in prostate cancer.
  • OTUD4 stabilizes MYH9 protein levels via deubiquitination, thereby inhibiting prostate cancer progression.
  • The OTUD4-MYH9 axis represents a promising therapeutic strategy for prostate cancer.

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