Abstract | BACKGROUND: METHODS: UBC cell lines and The Cancer Genome Atlas (TCGA) in-silico datasets were utilized to investigate UCHL1 expression pattern and functional as well as prognostic impacts in UBC cancer cell line models and patients. UCHL1 overexpression and silencing vectors and subsequent immunoprecipitation/ubiquitination experiments in combination of cellular functional assays were conducted to explore UCHL1-PKM2 interaction axis and its significance in UBC malignancy. RESULTS: UCHL1 was significantly up-regulated in UBC cancer cells and UCHL1 high-expression was associated with higher pathology/clinical grade and significantly inferior overall prognosis of UBC patients. UCHL1 interacted with PKM2 and enhanced PKM2 protein level through inhibition of PKM2 protein degradation via ubiquitination process. UCHL1-PKM2 interaction significantly promoted UBC cellular proliferation, metastasis and invasion activities. CONCLUSION: UCHL1-PKM2 interaction played an interesting role in UBC tumor cell proliferation, migration and metastasis. Our study suggests PKM2-targeted treatment might have a potential value in metastatic malignancy therapy development in the future.
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Authors | Yuhui Zheng, Dongliang Shi, Linlin Chen, Yinghong Yang, Meihong Yao |
Journal | Aging
(Aging (Albany NY))
Vol. 15
Issue 19
Pg. 10593-10606
(10 09 2023)
ISSN: 1945-4589 [Electronic] United States |
PMID | 37815895
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Ubiquitin Thiolesterase
- UCHL1 protein, human
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Topics |
- Humans
- Ubiquitin Thiolesterase
(genetics, metabolism)
- Cell Line, Tumor
- Urinary Bladder Neoplasms
(pathology)
- Carcinoma, Transitional Cell
- Cell Proliferation
(genetics)
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