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USP5 promotes tumor progression by stabilizing SLUG in bladder cancer
Qiang-Kun Wan1, Ting-Ting Li1, Bei-Bei Liu2
1Department of Radiotherapy, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui 233004, P.R. China.
Oncology Letters
|October 14, 2024
Summary
Ubiquitin-specific proteinase 5 (USP5) promotes bladder cancer progression by stabilizing SLUG, a key protein. Inhibiting USP5 shows potential for treating bladder cancer metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Urology
Background:
- Bladder cancer is a prevalent malignancy with invasive metastasis contributing significantly to mortality.
- The role of deubiquitinases, such as USP5, in cancer progression is increasingly recognized.
- USP5 has been implicated in the malignant progression of other cancers, including liver, colorectal, and lung cancer.
Purpose of the Study:
- To investigate the role and mechanism of ubiquitin-specific proteinase 5 (USP5) in the malignant progression of bladder cancer.
- To analyze the association between USP5 expression and bladder cancer prognosis and stage.
- To explore USP5's potential as a therapeutic target for bladder cancer.
Main Methods:
- Analysis of USP5 expression in The Cancer Genome Atlas database for correlation with bladder cancer prognosis and stage.
- Establishment of USP5-overexpressing and knockdown T24 bladder cancer cell lines.
- Assessment of cell viability, proliferation, and invasion using CCK-8, Transwell, and scratch assays.
- Evaluation of SLUG stability, USP5-SLUG interaction via immunoprecipitation and co-localization, and mRNA/protein levels via RT-qPCR and Western blotting.
- Treatment of bladder cancer cells with a USP5 inhibitor, Degrasyn.
Main Results:
- High USP5 expression in bladder cancer patients correlated with shorter survival and advanced clinicopathologic stage.
- USP5 overexpression in T24 cells increased proliferation, invasion, and epithelial-mesenchymal transition (EMT) markers.
- USP5 knockdown reduced proliferation, invasion, and EMT markers in T24 cells.
- USP5 directly binds to SLUG and upregulates its protein levels by inhibiting ubiquitination.
- Degrasyn treatment significantly inhibited T24 cell proliferation and invasion.
Conclusions:
- USP5 promotes bladder cancer malignant progression by stabilizing SLUG.
- USP5 is a potential therapeutic target for inhibiting bladder cancer progression and metastasis.
Keywords:
Snail family zinc finger 2bladder cancerepithelial-mesenchymal transitionubiquitin-specific proteinase 5More Related Videos
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