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To study effect of glutamine deprivation on the expression of genes encoding the key proliferation associated factors on a relation to inhibition of inositol requiring enzyme-1 IRE1 in U87 glioma cells was the aim of the research. It was shown that glutamine withdrawal down-regulated the expression of DEK, BRCA1, LIF, and COL6A1 genes in control glioma cells (transfected by empty vector), up-regulated ADGRE5 gene expression, and did not significantly change the expression of TPD52 and GNPDA. Inhibition of ІRE1 signaling enzyme activity modified the effect of glutamine deprivation on the expression of TPD52, BRCA1, LIF, DEK, ADGRE5, and COL6A1 genes: introduces the effect of glutamine deprivation on TPD52 and GNPDA1, reduced – on COL6A1, and enhanced – on ADGRE5, DEK, and BRCA1 in U87 glioma cells. Therefore, glutamine deprivation affect the expression level of most studied genes in U87 glioma cells in relation to the functional activity of IRE1 signaling enzyme, which is responsible for control of cell proliferation and glioma growth.

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) in U87 glioma cells. It was shown that the expression level of breast cancer 1 early onset (BRCA1) and tumor protein D52 (TPD52) mRNAs are strongly up-regulated in U87 glioma cells by down-regulation of IRE1 expression in comparison with the control cells. At the same time the expression level of collagen, type VI, alpha 1 (COL6A1), DEK oncogene (DEK), glucosamine-6-phosphate deaminase 1 (GNPDA1) and homer homolog 3 (HOMER3) was significantly down-regulated in glioma cells under these experimental conditions. It was also shown that hypoxia up-regulated the expression level of COL6A1 and TPD52 mRNAs and down-regulated – BRCA1, DEK, and GNPDA1 mRNAs in control glioma cells and that down-regulation of IRE1, which control cell proliferation and tumor growth, modified the effect of hypoxia on the expression of COL6A1, DEK, BCL2L1, HOMER3, and GNPDA1 genes. The present study demonstrated that hypoxia affected the expression of most studied genes in IRE1-dependent manner.