Downregulation of UBB potentiates SP1/VEGFA-dependent angiogenesis in clear cell renal cell carcinoma.
Jinpeng WangEnyang ZhaoBo GengWei ZhangZhuolun LiQing LiuWeiyang LiuWenfu ZhangWenbin HouNan ZhangZhiming LiuBosen YouPengfei WuXuedong LiPublished in: Oncogene (2024)
Clear cell renal cell carcinoma (ccRCC) presents a unique profile characterized by high levels of angiogenesis and robust vascularization. Understanding the underlying mechanisms driving this heterogeneity is essential for developing effective therapeutic strategies. This study revealed that ubiquitin B (UBB) is downregulated in ccRCC, which adversely affects the survival of ccRCC patients. UBB exerts regulatory control over vascular endothelial growth factor A (VEGFA) by directly interacting with specificity protein 1 (SP1), consequently exerting significant influence on angiogenic processes. Subsequently, we validated that DNA methyltransferase 3 alpha (DNMT3A) is located in the promoter of UBB to epigenetically inhibit UBB transcription. Additionally, we found that an unharmonious UBB/VEGFA ratio mediates pazopanib resistance in ccRCC. These findings underscore the critical involvement of UBB in antiangiogenic therapy and unveil a novel therapeutic strategy for ccRCC.
Keyphrases
- vascular endothelial growth factor
- endothelial cells
- end stage renal disease
- transcription factor
- dna methylation
- newly diagnosed
- ejection fraction
- chronic kidney disease
- single cell
- gene expression
- stem cells
- signaling pathway
- prognostic factors
- peritoneal dialysis
- protein kinase
- free survival
- amino acid
- smoking cessation
- tissue engineering