Glucose-dependent control of insulin like growth factor 2 mRNA binding protein 2 and other gene expressions in ERN1 knockdown glioblastoma cells

<b>Objective.</b> Endoplasmic reticulum stress and glucose supply are significant factors in glioblastoma growth. The present study aims to investigate the impact of glucose-dependent control of <i>IGF2BP2</i>, <i>TOB1</i>, <i>HBEGF</i>, <i>TWIST1</i>, <i>CCNH</i>, and <i>E2F1</i> gene expression in U87MG glioblastoma cells in response to the inhibition of both enzymatic activities of signaling protein ERN1. <b>Methods.</b> The U87MG glioblastoma cells with inhibited both enzymatic activities of ERN1 (endoribonuclease and protein kinase; dnERN1) were used. Cells transfected with an empty vector served as a control. The expression level of the <i>IGF2BP2</i> and other genes was studied by quantitative RT-PCR. <b>Results.</b> It was shown that the expression level of the <i>IGF2BP2</i> gene is up-regulated, while that of <i>TOB1</i> and <i>E2F1</i> genes is down-regulated in control glioblastoma cells treated with glucose deprivation. Nevertheless, the ERN1 knockdown modified the sensitivity of <i>IGF2BP2</i> and <i>TOB1</i> genes to reduced glucose supply. At the same time, the expression of <i>HBEGF</i>, <i>TWIST1</i>, and <i>CCNH</i> genes in control glioblastoma cells was resistant to glucose deprivation conditions. However, inhibition of the enzymatic activities of ERN1 signaling protein strongly increased the impact of glucose deprivation on <i>HBEGF</i> gene expression, but down-regulated the expression of the <i>TWIST1</i> gene. <b>Conclusion.</b> These results demonstrate that the enzymatic activity of signaling protein ERN1 controls the sensitivity of almost all studied genes to glucose deprivation in U87MG glioblastoma cells in a gene-specific manner. This is important for elucidating the endoplasmic reticulum stress-mediated sensitivity of key regulatory gene expression in glioblastoma cells to glucose supply, a significant factor in tumor growth.