Prognostic biomarker PSMD14 facilitates bladder cancer tumorigenesis and progression by regulating Nucleolin-YAP1 axis
Deubiquitinating enzymes (DUBs) significantly contribute to tumor progression and treatment resistance in bladder cancer. However, the mechanisms by which DUBs promote malignant behavior in patients with bladder cancer remain poorly understood. Using online databases such as TCGA, GSE13507, and GSE2...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-05-01
|
| Series: | Translational Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523325001019 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849769312276971520 |
|---|---|
| author | Yunfei Wu Zhijie Xu Runzhe Wang Yanfeng Bai Xiaoyi Chen Cheng Cheng Baiye Jin Guanghou Fu |
| author_facet | Yunfei Wu Zhijie Xu Runzhe Wang Yanfeng Bai Xiaoyi Chen Cheng Cheng Baiye Jin Guanghou Fu |
| author_sort | Yunfei Wu |
| collection | DOAJ |
| description | Deubiquitinating enzymes (DUBs) significantly contribute to tumor progression and treatment resistance in bladder cancer. However, the mechanisms by which DUBs promote malignant behavior in patients with bladder cancer remain poorly understood. Using online databases such as TCGA, GSE13507, and GSE23894, along with clinical sample validation, the expression profiles of PSMD14 in patients with bladder cancer were identified. The analysis revealed correlations among PSMD14, nucleolin (NCL), and YAP1, which were verified using TCGA data and clinical sample studies. In this study, PSMD14 was identified as a novel DUB involved in bladder cancer malignancy. PSMD14 expression is upregulated in the tissues of patients with bladder cancer and is associated with poor clinical outcomes. Both in vitro and in vivo experiments demonstrated that PSMD14 inhibition significantly reduced bladder cancer cell proliferation, metastasis, and cisplatin resistance. Mechanistic investigations revealed that PSMD14 enhances protein stability and NCL expression through deubiquitination. NCL, an RNA-binding protein, exerts oncogenic effects in patients with bladder cancer by binding to and stabilizing YAP1 mRNA, leading to increased YAP1 expression and activation of downstream YAP1-related pathways. Notably, the tumor-suppressive effects of PSMD14 inhibition were partially reversed by the overexpression of either NCL or YAP1. In conclusion, the PSMD14/NCL/YAP1 axis plays a pivotal role in the malignant behavior of bladder cancer, including proliferation, metastasis, and chemoresistance. These findings suggest that PSMD14 is a critical biomarker for predicting bladder cancer prognosis and is a potential target for therapeutic interventions. |
| format | Article |
| id | doaj-art-4dfb8a1255ed42f8afbf37ad7d430981 |
| institution | DOAJ |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj-art-4dfb8a1255ed42f8afbf37ad7d4309812025-08-20T03:03:27ZengElsevierTranslational Oncology1936-52332025-05-015510237010.1016/j.tranon.2025.102370Prognostic biomarker PSMD14 facilitates bladder cancer tumorigenesis and progression by regulating Nucleolin-YAP1 axisYunfei Wu0Zhijie Xu1Runzhe Wang2Yanfeng Bai3Xiaoyi Chen4Cheng Cheng5Baiye Jin6Guanghou Fu7Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; Zhejiang Engineering Research Center for Urinary Bladder Carcinoma Innovation Diagnosis and Treat-ment, Hangzhou 310024, ChinaDepartment of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; Zhejiang Engineering Research Center for Urinary Bladder Carcinoma Innovation Diagnosis and Treat-ment, Hangzhou 310024, ChinaDepartment of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; Zhejiang Engineering Research Center for Urinary Bladder Carcinoma Innovation Diagnosis and Treat-ment, Hangzhou 310024, ChinaDepartment of pathology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, ChinaDepartment of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; Zhejiang Engineering Research Center for Urinary Bladder Carcinoma Innovation Diagnosis and Treat-ment, Hangzhou 310024, ChinaDepartment of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; Zhejiang Engineering Research Center for Urinary Bladder Carcinoma Innovation Diagnosis and Treat-ment, Hangzhou 310024, ChinaDepartment of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; Zhejiang Engineering Research Center for Urinary Bladder Carcinoma Innovation Diagnosis and Treat-ment, Hangzhou 310024, China; Corresponding authors.Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; Zhejiang Engineering Research Center for Urinary Bladder Carcinoma Innovation Diagnosis and Treat-ment, Hangzhou 310024, China; Corresponding authors.Deubiquitinating enzymes (DUBs) significantly contribute to tumor progression and treatment resistance in bladder cancer. However, the mechanisms by which DUBs promote malignant behavior in patients with bladder cancer remain poorly understood. Using online databases such as TCGA, GSE13507, and GSE23894, along with clinical sample validation, the expression profiles of PSMD14 in patients with bladder cancer were identified. The analysis revealed correlations among PSMD14, nucleolin (NCL), and YAP1, which were verified using TCGA data and clinical sample studies. In this study, PSMD14 was identified as a novel DUB involved in bladder cancer malignancy. PSMD14 expression is upregulated in the tissues of patients with bladder cancer and is associated with poor clinical outcomes. Both in vitro and in vivo experiments demonstrated that PSMD14 inhibition significantly reduced bladder cancer cell proliferation, metastasis, and cisplatin resistance. Mechanistic investigations revealed that PSMD14 enhances protein stability and NCL expression through deubiquitination. NCL, an RNA-binding protein, exerts oncogenic effects in patients with bladder cancer by binding to and stabilizing YAP1 mRNA, leading to increased YAP1 expression and activation of downstream YAP1-related pathways. Notably, the tumor-suppressive effects of PSMD14 inhibition were partially reversed by the overexpression of either NCL or YAP1. In conclusion, the PSMD14/NCL/YAP1 axis plays a pivotal role in the malignant behavior of bladder cancer, including proliferation, metastasis, and chemoresistance. These findings suggest that PSMD14 is a critical biomarker for predicting bladder cancer prognosis and is a potential target for therapeutic interventions.http://www.sciencedirect.com/science/article/pii/S1936523325001019Bladder cancerPSMD14NCLProgression |
| spellingShingle | Yunfei Wu Zhijie Xu Runzhe Wang Yanfeng Bai Xiaoyi Chen Cheng Cheng Baiye Jin Guanghou Fu Prognostic biomarker PSMD14 facilitates bladder cancer tumorigenesis and progression by regulating Nucleolin-YAP1 axis Translational Oncology Bladder cancer PSMD14 NCL Progression |
| title | Prognostic biomarker PSMD14 facilitates bladder cancer tumorigenesis and progression by regulating Nucleolin-YAP1 axis |
| title_full | Prognostic biomarker PSMD14 facilitates bladder cancer tumorigenesis and progression by regulating Nucleolin-YAP1 axis |
| title_fullStr | Prognostic biomarker PSMD14 facilitates bladder cancer tumorigenesis and progression by regulating Nucleolin-YAP1 axis |
| title_full_unstemmed | Prognostic biomarker PSMD14 facilitates bladder cancer tumorigenesis and progression by regulating Nucleolin-YAP1 axis |
| title_short | Prognostic biomarker PSMD14 facilitates bladder cancer tumorigenesis and progression by regulating Nucleolin-YAP1 axis |
| title_sort | prognostic biomarker psmd14 facilitates bladder cancer tumorigenesis and progression by regulating nucleolin yap1 axis |
| topic | Bladder cancer PSMD14 NCL Progression |
| url | http://www.sciencedirect.com/science/article/pii/S1936523325001019 |
| work_keys_str_mv | AT yunfeiwu prognosticbiomarkerpsmd14facilitatesbladdercancertumorigenesisandprogressionbyregulatingnucleolinyap1axis AT zhijiexu prognosticbiomarkerpsmd14facilitatesbladdercancertumorigenesisandprogressionbyregulatingnucleolinyap1axis AT runzhewang prognosticbiomarkerpsmd14facilitatesbladdercancertumorigenesisandprogressionbyregulatingnucleolinyap1axis AT yanfengbai prognosticbiomarkerpsmd14facilitatesbladdercancertumorigenesisandprogressionbyregulatingnucleolinyap1axis AT xiaoyichen prognosticbiomarkerpsmd14facilitatesbladdercancertumorigenesisandprogressionbyregulatingnucleolinyap1axis AT chengcheng prognosticbiomarkerpsmd14facilitatesbladdercancertumorigenesisandprogressionbyregulatingnucleolinyap1axis AT baiyejin prognosticbiomarkerpsmd14facilitatesbladdercancertumorigenesisandprogressionbyregulatingnucleolinyap1axis AT guanghoufu prognosticbiomarkerpsmd14facilitatesbladdercancertumorigenesisandprogressionbyregulatingnucleolinyap1axis |