The deubiquitinase USP5 promotes cholangiocarcinoma progression by stabilizing YBX1
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View abstract on PubMed
Summary
This summary is machine-generated.Ubiquitin specific peptidase 5 (USP5) promotes cholangiocarcinoma (CCA) progression by stabilizing Y box-binding protein 1 (YBX1). Targeting the USP5-YBX1 axis offers a potential therapeutic strategy for CCA.
Area Of Science
- Oncology
- Molecular Biology
- Biochemistry
Background
- Ubiquitin specific peptidase 5 (USP5) is implicated in cancer progression.
- Cholangiocarcinoma (CCA) is a challenging malignancy with limited therapeutic options.
Purpose Of The Study
- To investigate the role and molecular mechanisms of USP5 in CCA.
- To explore USP5 as a potential therapeutic target for CCA.
Main Methods
- Gain-of-function and loss-of-function assays in CCA cell lines.
- Assessment of cell proliferation, migration, and tumorigenesis using CCK8, colony formation, EDU, flow cytometry, transwell assays, and xenografts.
- Western blot, immunohistochemistry, immunoprecipitation, immunofluorescence, ubiquitination, and cycloheximide chase assays to elucidate molecular mechanisms.
- Investigated the interaction and deubiquitination of Y box-binding protein 1 (YBX1) by USP5.
Main Results
- USP5 is highly expressed in CCA tissues and promotes cancer progression.
- USP5 knockdown inhibits CCA cell proliferation, migration, epithelial-mesenchymal transition (EMT), and tumor growth in vivo.
- USP5 stabilizes YBX1 through deubiquitination, hindering YBX1 phosphorylation and nuclear translocation.
- YBX1 silencing reverses the effects of USP5 overexpression in CCA cells.
Conclusions
- USP5 drives CCA cell proliferation, migration, and EMT by stabilizing YBX1.
- The USP5-YBX1 axis represents a promising therapeutic target for cholangiocarcinoma.
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