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Aberrant FBXW7-mediated ubiquitination and degradation of ZMYND8 enhances tumor progression and stemness in bladder cancer
- Source :
- Experimental Cell Research. 407:112807
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- ZMYND8, an epigenetic regulator, was identified as a common oncogene across various tumors. However, little was reported about the association between ZMYND8 and bladder cancer. Besides, aberrant mechanisms that contribute to abnormal ZMYND8 expressions still remain unclear. In the current study, we first found that ZMYND8 protein levels were significantly elevated in Bca samples versus normal tissues, but not the mRNA levels. We then utilized the Cell Counting Kit-8 (CCK-8) assay, clone formation assay and transwell analysis to confirm that ZMYND8 could remarkably promote the tumor progression in vitro, including growth capacity and migration. Bioinformatic predictive analysis revealed that E3 ubiquitin ligase FBXW7 interacts directly with ZMYND8 and degrades ZMYND8 in a polyubiquitination manner. Low FBXW7 was a hazard factor for promoting and depending on accumulated ZMYND8 proteins to promote Bca progression. Gene set enrichment analysis (GSEA) further indicated that ZMYND8 was notably associated with stemness process, which was well functionally validated. Lastly, ZMYND8 deficiency was observed to inhibit tumor growth of Bca in vivo, revealing a promising translational significance in Bca treatment. In conclusion, our study for the first time provided evidence for a novel mechanism of FBXW7/ZMYND8 axis in Bca, providing therapeutic vulnerability for individualized cancer treatment.
- Subjects :
- Male
F-Box-WD Repeat-Containing Protein 7
Regulator
Clone (cell biology)
Mice, Nude
Apoptosis
Mice
Ubiquitin
Biomarkers, Tumor
Tumor Cells, Cultured
medicine
Animals
Humans
Epigenetics
Cell Proliferation
Mice, Inbred BALB C
Bladder cancer
biology
Oncogene
Tumor Suppressor Proteins
Ubiquitination
Cell Biology
Prognosis
medicine.disease
Xenograft Model Antitumor Assays
Ubiquitin ligase
Gene Expression Regulation, Neoplastic
Survival Rate
Urinary Bladder Neoplasms
Tumor progression
Proteolysis
Neoplastic Stem Cells
biology.protein
Cancer research
Subjects
Details
- ISSN :
- 00144827
- Volume :
- 407
- Database :
- OpenAIRE
- Journal :
- Experimental Cell Research
- Accession number :
- edsair.doi.dedup.....b7601c401d37a2a6c529dd26a77639e5