Abstract
We have studied the expression of a subset of genes encoding important tumor growth related factors in U87 glioma cells with IRE1 (inositol requiring enzyme-1) knockdown as well as their hypoxic regulation. It was shown that the expression levels of activating transcription factor 6 (ATF6), clusterin (CLU), adhesion G protein-coupled receptor E5 (ADGRE5), transglutaminase 2, C polypeptide (TGM2), leukemia inhibitory factor (LIF), phosphoserine aminotransferase 1 (PSAT1), glyoxalase I (GLO1) and tetraspanin 13 (TSPAN13) are significantly down-regulated in glioma cells with the knockdown of IRE1 signaling enzyme. It was also shown that in glioma cells subjected to hypoxia, the expression levels of PSAT1, TSPAN13, EIF2AK3, and TGM2 genes were up-regulated, whereas the expression of ATF6 gene was down-regulated. At the same time, the expression levels of LIF, CLU, and ADGRE5 genes did not change in response to hypoxic treatment. Furthermore, inhibition of IRE1, a key effector of an unfolded protein response pathway, modified the effect of hypoxia on the expression of most studied genes. Present study demonstrates that IRE1 knockdown down-regulated the expression of most studied genes and modified their hypoxic regulation and that these changes possibly contributed to the suppression of glioma growth in cells without IRE1 signaling enzyme function.
Highlights
It was shown that the expression levels of activating transcription factor 6 (ATF6), clusterin (CLU), adhesion G protein-coupled receptor E5 (ADGRE5), transglutaminase 2, C polypeptide (TGM2), leukemia inhibitory factor (LIF), phosphoserine aminotransferase 1 (PSAT1), glyoxalase I (GLO1) and tetraspanin 13 (TSPAN13) are significantly down-regulated in glioma cells with the knockdown of IRE1 signaling enzyme
We have studied the effect of hypoxia on the expression of genes encoding EIF2AK3, ATF6, PSAT1, CLU, TGM2, ADGRE5, TSPAN13, LIF, and GLO1 proteins in U87 glioma cells in relation to inhibition of IRE1 signaling enzyme, Table 1
We have studied effect of hypoxia on the expression of EIF2AK3, ATF6, PSAT1, TSPAN13, TGM2, CLU, ADGRE5, LIF, and GLO1 genes in control U87 glioma cells and cells with IRE1 knockdown
Summary
The endoplasmic reticulum stress is an important regulator of glioblastoma multiforme growth [5] [6] [7] [8]. The endoplasmic reticulum stress modifies the expression of numerous regulatory and proliferation related genes, which are responsible for glioma growth [9] [13] [14] [15] [16]. Hypoxia is another important factor to glioma development, which promotes a more aggressive tumor behavior [17] [18]. The effect of hypoxia on the expression levels of a vast number of genes in glioma cells is dependent on IRE1 signaling enzyme function [16] [21] [22]
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