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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2016; 62(1): 3-15

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

  1. Palladin Institute of Biochemistry National Academy of Sciences of Ukraine, Kyiv, Ukraine
  2. O.O. Bogomolets National Medical University, Kyiv, Ukraine


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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