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.
References
[1]
Gyongyan, S.A., Manucharyan, T.G., Danielyan, K.E., Kevorkyan, G.A. and Chailyan, S.G. (2013) Xanthine Oxidoreductase Is a Key Enzyme of Purine Catabolism Regulation. Electronic Journal of Natural Science, 2, 17-21.
[2]
Danielyan, K.E. and Kevorkian, G.A. (2011) Xanthine Oxidase Activity Regulates Human Embryonic Brain Cells Growth. Biopolymer and Cell, 27, 350-353. https://doi.org/10.7124/bc.000121
[3]
Danielyan, K.E. (2013) Dependence of Cells Survival from Xanthine Oxidase and Dihydopyrimidine Dehydrogenase Correlative Activities in Human Brain Derived Cell Culture. Central Nervous System Agents in Medicinal Chemistry, 13, 108-113. https://doi.org/10.2174/1871524911313020003
[4]
Aganyants, H.A., Abrahamyan, R.A., Chailyan, S.G., et al. (2014) New Highlights in the Regulation of Cells Proliferation. Neuroscience and Biomedical Engineering, 2, 81-86. https://doi.org/10.2174/2213385203666150213190534
[5]
Wang, X., Yang, K. and Xie, Q. (2017) Purine Synthesis Promotes Maintenance of Brain Tumor Initiating Cells in Glioma. Nature Neuroscience, 20, 661-673. https://doi.org/10.1038/nn.4537
[6]
Danielyan, K.E., Babayan, L.A. and Chailyan, S.G. (2019) Delineation of Effectors Impact on the Human Brain Derived Phosphoribosylpyrophosphate Synthetase Activity. Biomedical Journal of Scientific and Technical Research, 24, 17918-17926. https://doi.org/10.26717/BJSTR.2019.24.003988
[7]
Danielyan, K.E., Vardanyan, R., Paronyan, Z.K., Barkhudaryants, I.M., Bisharyan, M.S. and Chailyan, S.G. (2018) PRPS-1 Is a Regulative for Neuroprotection and Cells Regenerative Proliferation. Journal of Biomolecules and Biochemistry, 2, 6-10.
[8]
Lindsey, S. and Langhans, S.A. (2015) Epidermal Growth Factor Signaling in Transformed Cells. International Review of Cell and Molecular Biology, 314, 1-41. https://doi.org/10.1016/bs.ircmb.2014.10.001
Vivanco, I. and Sawyers, C.L. (2002) The Phosphatidylinositol 3-Kinase AKT Pathway in Human Cancer. Nature Reviews Cancer, 2, 489-501. https://doi.org/10.1038/nrc839
[11]
Niu, G., Wright, K.L., Huang, M., et al. (2002) Constitutive Stat3 Activity Up-Regulates VEGF Expression and Tumor Angiogenesis. Oncogene, 21, 2000-2008. https://doi.org/10.1038/sj.onc.1205260
[12]
Patterson, R.L., van Rossum, D.B., Nikolaidis, N., et al. (2005) Phospholipase C-Gamma: Diverse Roles in Receptor-Mediated Calcium Signaling. Trends in Biochemical Sciences, 30, 688-697. https://doi.org/10.1016/j.tibs.2005.10.005
[13]
Ye, D.Z. and Field, J. (2012) PAK Signaling in Cancer. Cellular Logistics, 2, 105-116. https://doi.org/10.4161/cl.21882
[14]
Yu, P., Fan, Y., Qu, X., et al. (2016) Cbl-b Regulates the Sensitivity of Cetuximab through Ubiquitin-Proteasome System in Human Gastric Cancer Cells. Journal of BUON, Journal of Balkan Union of Oncology, 21, 867-873.
[15]
Sigoillot, F.D., Berkowski, J.A., Sigoillot, S.M., et al. (2003) Cell Cycle-Dependent Regulation of Pyrimidine Biosynthesis. The Journal of Biological Chemistry, 278, 3403-3409. https://doi.org/10.1074/jbc.M211078200
[16]
Danielyan, K.E. (2017) Egf Regulates Purine and Pyrimidine Metabolism. Journal of Biomolecules and Biochemistry, 1, In Press. https://www.pulsus.com/journal-biomolecules-biochemistry/inpress.html
[17]
Zollnerd, N. (1982) Purine and Pyrimidine Metabolism. Proceedings of the Nutrition Society, 41, 329-342. https://doi.org/10.1079/PNS19820048
[18]
Thakkar, J.P., Dolecek, T.A., Horbinski, C., Ostrom, Q.T., Lightner, D.D., Barnholtz-Sloan, J.S. and Villano, J.L. (2014) Epidemiologic and Molecular Prognostic Review of Glioblastoma. Cancer Epidemiology, Biomarkers and Prevention, 23, 1985-1996. https://doi.org/10.1158/1055-9965.EPI-14-0275
[19]
Phillips,, H.S., Kharbanda, S., Chen, R., Forrest, W.F., Soriano, R.H., Wu, T.D. and Aldape, K. (2006) Molecular Subclasses of High-Grade Glioma Predict Prognosis, Delineate a Pattern of Disease Progression, and Resemble Stages in Neurogenesis. Cancer Cell, 9, 157-173. https://doi.org/10.1016/j.ccr.2006.02.019