Expression of proliferation related transcription factor genes in U87 glioma cells with IRE1 knockdown: upon glucose and glutamine deprivation
D.O. Tsymbal1, D.O. Minchenko1,2, I.V. Kryvdiuk1, O.O. Riabovol1, O.V. Halkin1, O.O. Ratushna1, O.H. Minchenko1
- Palladin Institute of Biochemistry National Academy of Sciences of Ukraine, Kyiv, Ukraine
- O.O. Bogomolets National Medical University, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz62.01.003
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.
Keywords:
mRNA expression;transcription factors; endoplasmic reticulum stress;IRE1 inhibition; glucose deprivation; glutamine deprivation;glioma cells
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