Activation of pentose phosphate pathway is an important factor of enhanced cell proliferation and tumor growth. Phosphoribosyl pyrophosphate synthetase (PrPS) is a key enzyme of this pathway and plays a central role in the synthesis of purines and pyrimidines. Hypoxia as well as erN1 (from endoplasmic reticulum to nuclei-1) mediated endoplasmic reticulum stress response-signalling pathway is linked to the proliferation because the blockade of erN1 suppresses tumor growth, including glioma. We studied the expression of different PrPS genes in glioma cells with erN1 knockdown under hypoxic condition. It was shown that hypoxia decreases the expression of PrPS1 and PrPS2 genes in both types of glioma cells, being more pronounced in cells without erN1 function, but PrPSAP1 and PrPSAP2 gene expressions are suppressed by hypoxia only in glioma cells with blockade of erN1. Moreover, the blockade of endoribonuclease activity of erN1 does not affect the expression of PrPS1 and PrPS2 as well as PPrS-associated protein genes in U87 glioma cells. At the same time, the induction of endoplasmic reticulum stress by tunicamycin in glioma cells with suppressed activity of erN1 endoribonuclease decreases the expression level of PrPS1 and PrPS2 genes only. results of this investigation clearly demonstrated that the expression of different genes encoding subunits of PRPS enzyme is affected by hypoxia in U87 glioma cells, but the effect of hypoxia is modified by suppression of endoplasmic reticulum stress signaling enzyme erN1.

We have studied the effect of hypoxia on the expression level of mRNA of the basic enzymes of pentosephosphate cycle (G6PD, TKT, TALDO1,

Nutrient deprivation conditions are capable to induce the endoplasmic reticulum stress and are responsible for regulation of the expression of numerous growth factors which control the cell proliferation and angiogenesis in malignant tumors, including glioma. The ERN1 mediated endoplasmic reticulum stress response-signalling pathway is tightly linked to the proliferation because the blockade of ERN1 function suppresses the tumor growth via specific changes in the cell transcriptome. Activation of the pentose phosphate pathway is an important factor of enhanced cell proliferation and tumor growthbecause it controls the synthesis of nucleotides and respectively nucleic acids. We studied the effect of blockade the ERN1 signaling enzyme function in glioma cells on the expression of phosphoribosyl pyrophosphate synthetase (PRPS), an important enzyme of pentose phosphate pathway, as well as its dependence of glucose and glutamine deprivation.

We have studied the effect of IRE1 signaling enzyme knockdown as well as hypoxia on the expression of genes encoding the important tumor growth related proteins (BRCA1, DEK, BCL2L1, COL6A1, TPD52, HOMER3, and GNPDA1)