Expression of proliferation related transcription factor genes in U87 glioma cells with IRE1 knockdown: upon glucose and glutamine deprivation

Abstract

Glycolysis and glutaminolysis as well as endoplasmic reticulum stress are required for tumor progression suggests through regulation of the cell cycle. Inhibition of ERN1/IRE1 (endoplasmic reticulum to nucleus signaling 1/inositol requiring enzyme 1), a central mediator of endoplasmic reticulum stress, significantly suppresses glioma cell proliferation and tumor growth as well as modifies sensitivity gene expressions to glucose and glutamine deprivation. We have studied the expression of genes encoded transcription factors such as E2F8 (E2F transcription factor 8), EPAS1 (endothelial PAS domain protein 1), HOXC6 (homeobox C6), TBX3 (T-box 3), TBX2 (T-box 2), GTF2F2 (general transcription factor IIF), GTF2B (general transcription factor IIB), MAZ (MYC-associated zinc finger protein, purine-binding transcription factor), SNAI2 (snail family zinc finger 2), TCF3 (transcription factor 3), and TCF8/ZEB1 (zinc finger E-box binding homeobox 1)in U87 glioma cells upon glucose and glutamine deprivation in relation to inhibition of IRE1.We demonstrated that glutamine deprivation leads to up-regulation of the expression of EPAS1, TBX3, GTF2B, and MAZ genes and down-regulation of E2F8, GTF2F2, TCF8, and TBX2 genes in control glioma cells.At the same time, glucose deprivation enhances the expression of EPAS1 and GTF2B genes and decreases of E2F8, HOXC6, TCF3, and TBX2 genes in these glioma cells. Inhibition of IRE1 by dnIRE1 significantly modifies the expression most of studied genes with different magnitude. Present study demonstrates that fine-tuning of the expression of proliferation related transcription factor genes depends upon glucose and glutamine deprivation in IRE1-dependent manner and possibly contributes to slower tumor growth after inhibition of IRE1.

ERN1 modifies the effect of glutamine deprivation on tumor growth related factors expression in U87 glioma cells

“…Previously was shown that glutamine withdrawal affected the expression of several tumor growth related genes and that the effect of glutamine deprivation on most of these genes expression is dependent on ERN1 signaling enzyme function [19][20][21][22][23]. However, the regulation of the expression of many other tumor growth related genes by glutamine deprivation in relation to inhibition of ERN1 to not to be clarified yet.…”

The impact of glutamine deprivation on the expression of MEIS3, SPAG4, LHX1, LHX2, and LHX6 genes in ERN1 knockdown U87 glioma cells

“…Glutamine, as a substrate for glycolysis, is an important for the development and a more aggressive behavior of gliomas, which are highly aggressive tumors with very poor prognosis (Colombo et al 2011;Yalcin et al 2014;Zhao et al 2017;Alimohammadi et al 2020). Glutamine supply and endoplasmic reticulum stress are very important and complementary factors for the tumor growth and inhibition of ERN1/IRE1 (endoplasmic reticulum to nucleus signaling 1/inositol requiring enzyme 1) mediated stress signaling can significantly modify the effects of glutamine deprivation on some gene expressions (Minchenko et al 2013(Minchenko et al , 2015a(Minchenko et al , 2021Tsymbal et al 2016). It has been shown that ERN1 -XBP1 pathway is also essential for the glucose response and protection of β cells (Riabovol et al 2019).…”

“…Transcription factors play an important role in malignant tumor growth preferentially through ERN1 (endoplasmic reticulum to nucleus signaling 1) signaling pathway of endoplasmic reticulum stress (Minchenko et al 2015b(Minchenko et al , 2015cTsymbal et al 2016). The homeobox proteins represent an important group of transcription factors, which are related to tumorigenesis and are largely investigated (Guca et al 2018;Le Magnen et al 2018;Miyashita et al 2018;Hamaidi et al 2019;Li et al 2019).…”

General Transcription Factor IIF Polypeptide 2: A Novel Therapeutic Target for Depression Identified Using an Integrated Bioinformatic Analysis

“…After WGCNA and protein–protein interaction (PPI) analysis, general transcription factor IIF polypeptide 2 ( GTF2F2 ) was identified as the hub gene. GTF2F2 combines with general transcription factor IIF polypeptide 1 (GTF2F1) to form a heteromeric general transcription initiation factor (TFIIF), which subsequently binds to DNA-dependent RNA polymerase II ( Sasaki et al, 2013 ; Tsymbal et al, 2016 ). RNA polymerase II plays a critical role in mRNA synthesis, and GTF2F2 is essential for the initiation and elongation phases of gene transcription ( Sasaki et al, 2013 ).…”