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ARTICLE

OTUD4 Inhibits Prostate Cancer by Deubiquitinating MYH9

Zheng Qin1,2,#, Yueyao Zhang3,#, Dongze Liu4,#, Xiaokang Zheng5, Kaibin Wang1,2, Xiao Zhu1,2, Yuanhao Zhang1,2, Kexin Xu1,2, Changying Li1,2, Lijuan Kang1,2, Lili Wang1,2, Haitao Wang1,2,*
1 Tianjin Key Laboratory of Precision Medicine for Sex Hormones and Diseases, The Second Hospital of Tianjin Medical University, Tianjin, 300211, China
2 Department of Oncology, The Second Hospital of Tianjin Medical University, Tianjin, 300211, China
3 Department of Cell Biology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
4 Department of Urology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, 150001, China
5 Department of Urology, The Henan Provincial People’s Hospital, Zhengzhou, 462000, China
* Corresponding Author: Haitao Wang. Email: email
# These authors contributed equally to this work
(This article belongs to the Special Issue: Novel Biomarkers and Treatment Strategies in Solid Tumor Diagnosis, Progression, and Prognosis (Ⅱ))

Oncology Research https://doi.org/10.32604/or.2025.073455

Received 18 September 2025; Accepted 23 December 2025; Published online 14 January 2026

Abstract

Objective: Prostate cancer is the second most common fatal cancer in men. Identifying new biological therapeutic targets is crucial to effectively improve the prognosis of prostate cancer patients. Ovarian tumor family deubiquitinase 4 (OTUD4) is a member of the ovarian tumor-associated protease domain (OTUDs) family. Although previous studies have shown that the expression and function of OTUD4 vary across different tumors, its role in prostate cancer remains unknown. The aim of this study is to explore new therapeutic targets and diagnostic markers for prostate cancer and investigate their mechanisms of action. Methods: Cell culture, Cell Counting Kit-8 (CCK-8) assay, colony formation assay, Transwell assay, 5-Ethynyl-2′-deoxyuridine (EdU) assay, immunofluorescence, Western blot, Quantitative real-time PCR (qRT-PCR), protein mass spectrometry, nude mouse xenograft models, immunohistochemistry (IHC), and hematoxylin and eosin (H&E) staining were utilized. Results: We found that OTUD4 expression was reduced in prostate cancer and negatively correlated with poor prognosis in both in vivo and in vitro experiments. Subsequent mechanistic studies revealed that OTUD4 directly inhibits the degradation of myosin-9 (MYH9) protein via deubiquitination. Although MYH9 has been previously reported to act as a tumor suppressor in prostate cancer, no experimental evidence had demonstrated that MYH9 inhibits prostate cancer growth. Our results indicate that MYH9 overexpression effectively suppresses prostate cancer through interactions with cell adhesion molecules. Conclusion: Collectively, these results suggest that OTUD4 functions as a tumor suppressor in prostate cancer. Specifically, OTUD4 inhibits MYH9 degradation via deubiquitination, thereby enabling MYH9-mediated suppression of prostate cancer.

Keywords

Prostate cancer; ovarian tumor family deubiquitinase 4 (OTUD4); therapeutic target; myosin-9 (MYH9); ubiquitin (UB)

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