Repressive regulatory function of seryl-tRNA synthetase on VEGFA gene expression is impaired in renal cell carcinoma

Aim To assess the relationship of the mRNA and protein expression levels of seryl-tRNA synthetase (SerRS) and the expression of gene encoding vascular endothelial growth factor A (VEGFA) in patients with renal cell carcinoma (RCC). Methods Expression levels of VEGFA and SerRS mRNA were quantified by quantitative real-time polymerase chain reaction in 31 paired RCC tumor and adjacent healthy kidney tissues, while SerRS protein levels were assessed by western blot analysis in 19 paired samples. The association of SerRS and VEGFA with clinicopathological parameters was evaluated. In addition, bioinformatics analyses were performed using publicly available transcriptomic and proteomic data sets. Results VEGFA expression was significantly higher in tumor tissues than in adjacent healthy tissues, while SerRS mRNA levels were similar in both. However, SerRS protein was significantly elevated in tumor tissues. Despite elevated levels of SerRS protein in RCC tumor tissues, SerRS repressive regulatory function on VEGFA was impaired. This dysregulation was associated with increased SerRS phosphorylation, upregulation of several transcriptional activators, and hypomethylation of the VEGFA promoter – factors likely contributing to VEGFA overexpression. Importantly, higher SerRS gene expression was significantly associated with improved overall survival in patients. Conclusion The findings indicate that various factors diminish SerRS repressor function leading to the VEGFA upregulation in RCC. Survival analysis suggests that SerRS may serve as a valuable prognostic biomarker and represent a potential therapeutic target in RCC.