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

Objective. 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 IGF2BP2, TOB1, HBEGF, TWIST1, CCNH, and E2F1 gene expression in U87MG glioblastoma cells in response to the inhibition of both enzymatic activities of signaling protein ERN1. Methods. 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 IGF2BP2 and other genes was studied by quantitative RT-PCR. Results. It was shown that the expression level of the IGF2BP2 gene is up-regulated, while that of TOB1 and E2F1 genes is down-regulated in control glioblastoma cells treated with glucose deprivation. Nevertheless, the ERN1 knockdown modified the sensitivity of IGF2BP2 and TOB1 genes to reduced glucose supply. At the same time, the expression of HBEGF, TWIST1, and CCNH 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 HBEGF gene expression, but down-regulated the expression of the TWIST1 gene. Conclusion. 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.