Abstract
We were aiming to delineate, by the utility of the biological data results, in our investigations the link between the purine and pyrimidine metabolism and development of the glioblastoma. We analyzed the sets of the genes, belonging to the purine and pyrimidine metabolism by the utility of GSEA software as well as MSIgnDB application of the GSEA. The GEO database, GEOR2 tools were serving for the visualization of the genes expression profiles of the disease. The Cancer Proteome Atlas as well as the tools of the data sets were also used to collect and analyze the results. We concluded and came to the following consequential results. 1) Neurogenesis and Glioblastoma are sharing some common genes. 2) Purine and pyrimidine metabolism-linked enzymes and genes are responsible for the upregulation of DNA and mRNA synthesis in the settings of the tumor development. 3) EGFR expression responsible genes, mRNA as well as protein is upregulated during the development of the glioblastoma. 4) GMPS genes are more strongly upregulated in the settings of the glioblastoma than ADSL. 5) PRPS1 is strongly synthetized in neurospheres in contrast to the mature tissue during glioblastoma development.
Highlights
IntroductionWe have proved experimentally, by the inhibition of the Xanthine Oxidoreductase (EC 1.17.3.2), the one of the last and the key regulative enzymes in the chain of the purines catabolism-responsible enzymes, by its classical compound-Allopurinol, it is possible to decrease the speed of purines decay [1] [2]
We were aiming to delineate in our investigations, by the utility of the biological data results, the link between the purine and pyrimidine metabolism and development of glioblastoma.In our previous experiments, we have proved experimentally, by the inhibition of the Xanthine Oxidoreductase (EC 1.17.3.2), the one of the last and the key regulative enzymes in the chain of the purines catabolism-responsible enzymes, by its classical compound-Allopurinol, it is possible to decrease the speed of purines decay [1] [2]
2) Purine and pyrimidine metabolism-linked enzymes and genes are responsible for the upregulation of DNA and mRNA synthesis in the settings of the tumor development
Summary
We have proved experimentally, by the inhibition of the Xanthine Oxidoreductase (EC 1.17.3.2), the one of the last and the key regulative enzymes in the chain of the purines catabolism-responsible enzymes, by its classical compound-Allopurinol, it is possible to decrease the speed of purines decay [1] [2]. The group of the scientists in 2017 published the data, proving the elevation of purine metabolism in the brain tumor initiating cells (BTICs) is high, in contrast to the already differentiated glioma cells (DGCs). The authors concluded, the expression levels of three purine synthesis-responsible enzymes, PRPS1 (Phosphoribosyl pyrophosphate synthetase 1; EC 2.7.6.1), ADSL (Adenylosuccinatelyase; EC 4.3.2.2.) and GMPS (GMP synthetase EC 6.3.5.2) —each representing an arm of the purine biosynthesis pathway—were significantly elevated in BTICs (Brain Tumor Initiating Cells) as compared to matched DGCs (Differentiated Glioma Cells) [5]. Activities of the mentioned enzymes were elevated [6]
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