engleski

Is expression of VEGFA gene regulated by seryl-tRNA synthetase in renal cell carcinoma?

Aminoacyl-tRNA synthetases are essential enzymes that charge tRNA with the cognate amino acid providing substrates for ribosomal protein biosynthesis. Except for this canonical function, recent studies indicate their noncanonical role in a large number of human diseases, including cancer. It is known that vertebrate seryl-tRNA synthetase (SerRS) can enter the nucleus where it downregulates expression of vascular endothelial growth factor A (VEGFA), key regulator of angiogenesis. VEGFA expression is upregulated in many tumors, enhancing angiogenesis and tumor development. Considering that decreased expression of SerRS leads to upregulation of VEGFA in human cell lines, SerRS may be implicated in carcinogenesis. Indeed, it was previously shown that SerRS expression in prostate cancer was downregulated. In this study, interplay of SerRS and VEGFA expression was examined in another urogenital type of cancer, clear cell renal cell carcinoma (ccRCC), most common prevalent molecular subtype of kidney cancer. ccRCC tissue samples and matched adjacent nontumor renal tissue samples were obtained from patients who underwent radical or partial nephrectomy. VEGFA and SerRS gene expression levels were examined using RT-qPCR, while SerRS protein levels were analyzed by western blot, in both tumor and nontumor tissue. Data analysis showed elevated levels of VEGFA mRNA in tumor tissue, however there was no correlation between SerRS and VEGFA expression. Therefore, it appears that SerRS does not participate in regulation of VEGFA gene expression in ccRCC and that upregulation of VEGFA is caused via other cellular mechanisms.

aminoacyl-tRNA synthetase ; VEGFA ; kidney

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