Tag Archives: glioma cells
Hypoxic regulation of MYBL1, MEST, TCF3, TCF8, GTF2B, GTF2F2 and SNAI2 genes expression in U87 glioma cells upon IRE1 inhibition
O. H. Minchenko1, D. O. Tsymbal1, D. O. Minchenko1,2, O. O. Kubaychuk3
1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: ominchenko@yahoo.com;
2Bohomolets National Medical University, Kyiv, Ukraine;
3National University of Food Technologies, Kyiv, Ukraine
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 did not affect the expression of TCF3 and GTF2B transcription factor genes. In turn, inhibition of IRE1 modified the effect of hypoxia on the expression of all studied genes, except MYBL1 and GTF2B. For instance, IRE1 knockdown decreased sensitivity to hypoxia of the expression of MEST, TCF8 and SNAI2 genes and increased sensitivity to hypoxia of GTF2F2 expression. At the same time, IRE1 inhibition introduced sensitivity to hypoxia of the expression of TCF3 gene in glioma cells. The present study demonstrated that the inhibition of IRE1 in glioma cells affected the hypoxic regulation of the expression of studied genes in various directions, though hypoxic conditions did 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 magnified the effect of IRE1 inhibition on the expression of respective genes in glioma cells.
The role of the TNF receptors and apoptosis inducing ligands in tumor growth
O. H. Minchenko1, D. O. Tsymbal1, D. O. Minchenko1,2, О. O. Ratushna1
1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: ominchenko@yahoo.com;
2Bohomolets National Medical University, Kyiv, Ukraine
Tumor necrosis factor (TNF) superfamily receptors and TNF apoptosis inducing ligands play an important role in the realization of TNF function and control tumor growth. The TNF-related pathways are controlled by endoplasmic reticulum stress signaling, which has a crucial role in the control of cell proliferation and tumor growth. Furthermore, the inhibition of IRE1 (inositol requiring enzyme-1), which is a central mediator of endoplasmic reticulum stress sand mainly responsible for cell proliferation and apoptosis, leads to suppression of tumor growth through specific changes in the expression of genes encoding transcription factors, tumor suppressors, angiogenesis and apoptosis related proteins, including TNF superfamily receptors and TNF apoptosis inducing ligands. Therefore, changes in the expression level of TNF-related genes encoding TNF superfamily receptors and apoptosis inducing ligands possibly reflect metabolic reprogramming of cancer cells upon inhibition of IRE1-mediated endoplasmic reticulum stress signaling and correlate with suppression of glioma cell proliferation.
Expression of IGFBP6, IGFBP7, NOV, CYR61, WISP1 and WISP2 genes in U87 glioma cells in glutamine deprivation condition
O. H. Minchenko1, A. P. Kharkova1, D. O. Minchenko1,2, L. L. Karbovskyi1
1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: ominchenko@yahoo.com;
2Bohomolets National Medical University, Kyiv, Ukraine
We have studied gene expression of insulin-like growth factor binding proteins in U87 glioma cells upon glutamine deprivation depending on the inhibition of IRE1 (inositol requiring enzyme-1), a central mediator of endoplasmic reticulum stress. We have shown that exposure of control glioma cells upon glutamine deprivation leads to down-regulation of NOV/IGFBP9, WISP1 and WISP2 gene expressions and up-regulation of CYR61/IGFBP10 gene expression at the mRNA level. At the same time, the expression of IGFBP6 and IGFBP7 genes in control glioma cells was resistant to glutamine deprivation. It was also shown that the inhibition of IRE1 modifies the effect of glutamine deprivation on the expression of all studied genes. Thus, the inhibition of IRE1 signaling enzyme enhances the effect of glutamine deprivation on the expression of CYR61 and WISP1 genes and suppresses effect of the deprivation on WISP2 gene expression in glioma cells. Moreover, the inhibition of IRE1 introduces sensitivity of the expression of IGFBP6 and IGFBP7 genes to glutamine deprivation and removes this sensitivity to NOV gene. We have also demonstrated that the expression of all studied genes in glioma cells growing with glutamine is regulated by IRE1 signaling enzyme, because the inhibition of IRE1 significantly down-regulates IGFBP6 and NOV genes and up-regulates IGFBP7, CYR61, WISP1, and WISP2 genes as compared to control glioma cells. The present study demonstrates that glutamine deprivation condition affects most studied IGFBP and WISP gene expressions in relation to IRE1 signaling enzyme function and possibly contributes to slower glioma cell proliferation upon inhibition of IRE1.