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Updated: May 10, 2026
A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
Published on: March 15, 2016
Repressive regulatory function of seryl-tRNA synthetase on VEGFA gene expression is impaired in renal cell carcinoma
Maja Barači, Petar Ozretić, Marijana Knezovic
1Jasmina Rokov-Plavec, Department of Chemistry, Faculty of Science, Horvatovac 102a, 10000 Zagreb, Croatia, rokov@chem.pmf.hr.
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.
Insights
In renal cell carcinoma (RCC), impaired seryl-tRNA synthetase (SerRS) function leads to increased vascular endothelial growth factor A (VEGFA) expression. Higher SerRS gene expression correlates with better patient survival, suggesting its potential as a prognostic biomarker.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Renal cell carcinoma (RCC) is a significant health concern with complex molecular underpinnings.
- Vascular endothelial growth factor A (VEGFA) is a key driver of angiogenesis and tumor growth in various cancers, including RCC.
- Seryl-tRNA synthetase (SerRS) is an enzyme with known roles beyond translation, including potential regulatory functions.
Purpose of the Study:
- To investigate the relationship between seryl-tRNA synthetase (SerRS) and vascular endothelial growth factor A (VEGFA) expression in renal cell carcinoma (RCC).
- To determine if SerRS and VEGFA expression levels correlate with clinicopathological parameters in RCC patients.
- To explore the prognostic significance of SerRS in RCC.
Main Methods:
- Quantitative real-time polymerase chain reaction (qPCR) was used to measure VEGFA and SerRS mRNA levels in paired RCC tumor and adjacent healthy kidney tissues.
- Western blot analysis was performed to assess SerRS protein levels in a subset of paired samples.
- Bioinformatics analyses utilized publicly available transcriptomic and proteomic datasets to further investigate molecular associations.
Main Results:
- VEGFA mRNA and protein expression were significantly elevated in RCC tumor tissues compared to healthy kidney tissues.
- While SerRS mRNA levels were similar, SerRS protein levels were significantly higher in tumor tissues.
- Despite increased SerRS protein, its repressive function on VEGFA was impaired in RCC tumors, associated with increased SerRS phosphorylation and VEGFA promoter hypomethylation, leading to VEGFA overexpression.
- Higher SerRS gene expression was significantly associated with improved overall survival in RCC patients.
Conclusions:
- Dysregulation of SerRS's repressor function, influenced by factors like phosphorylation and epigenetic modifications, contributes to VEGFA overexpression in RCC.
- SerRS demonstrates potential as a valuable prognostic biomarker for improved survival in renal cell carcinoma.
- SerRS represents a potential therapeutic target for the management of RCC.
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