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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.
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.
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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