IRE1 KNOCKDOWN MODIFIES GLUCOSE AND GLUTAMINE DEPRIVATION EFFECTS ON THE EXPRESSION OF PROLIFERATION RELATED GENES IN U87 GLIOMA CELLS

We have studied the expression of genes encoding proliferation related factors and enzymes such as IL13RA2, KRT18, CD24, ING1, ING2, MYL9,BET1,TRAPPC3, ENDOG, POLG, TSFM, and MTIF2 in U87 glioma cells upon glucose and glutamine deprivation in relation to inhibition of inositol requiring enzyme 1, a central mediator of endoplasmic reticulum stress. It was shown that glutamine deprivation leads to up-regulation of the expression of BET1, MYL9, and MTIF2 genes and down-regulation of CD24, ING2, ENDOG, POLG, and TSFM genes in control (with native IRE1) glioma cells. At the same time, glucose deprivation enhances the expression of MYL9 gene only and decreases - ING1, ING2, and MTIF2 genes in control glioma cells. Thus, effect of glucose and glutamine deprivation on gene expressions in glioma cells is gene-specific. Inhibition of inositol requiring enzyme 1 by dnIRE1 significantly modifies the effect of both glutamine and glucose deprivation on the expression of most studied genes with different direction and magnitude, especially for ING2, CD24, and MTIF2 genes. Present study demonstrates that IRE 1 knockdown modifies glucose and glutamine deprivation effects on the expression of proliferation related genes and possibly contributes to slower tumor growth of these glioma cells after inhibition of IRE1 signaling enzyme.