Hypoxic regulation of MYBL1, MEST, TCF3, TCF8, GTF2B, GTF2F2 and SNAI2 genes expression in U87 glioma cells upon ire1 inhibition

Abstract

We investigated the impact of IRE1/ERN1 (inositol requiring enzyme 1/endoplasmic reticulum to nucleus signaling 1) knockdown on hypoxic regulation of the expression of a subset of proliferation and migration- related genes in U87 glioma cells. It was shown that hypoxia leads to up-regulation of the expression of MEST and SNAI2, to down-regulation – of MYBL1, TCF8 and GTF2F2 genes at the mRNA level in control glioma cells. At the same time hypoxia does not affect the expression of TCF3 and GTF2B transcription factor genes. In turn, inhibition of IRE1 modifies the effect of hypoxia on the expression of all studied genes, except MYBL1 and GTF2B. For instance, IRE1 knockdown decreases sensitivity to hypoxia of the expression of MEST, TCF8 and SNAI2 genes and increases sensitivity to hypoxia of GTF2F2 expression. At the same time IRE1 inhibition introduces sensitivity to hypoxia of the expression of TCF3 gene in glioma cells. The present study demonstrates the inhibition of IRE1 in glioma cells affects the hypoxic regulation of the expression of genes studied. Hypoxic conditions do not abolish the effect of IRE1 inhibition on the expression of respective genes. To the contrary, in case of SNAI2, GTF2F2 and MEST hypoxic conditions magnify the effect of IRE1 inhibition on the expression of respective genes in glioma cells.