Tag Archives: glioblastoma cells
Endoplasmic reticulum stress differentially alters the effect of hypoxia on PSAT1 and CYCLIN D1 gene expressions in normal astrocytes and glioblastoma cells
Y. M. Viletska*, M. Y. Sliusar, A. I. Abramchuk, O. V. Halkin,
O. O. Ratushna, O. Y. Luzina, O. H. Minchenko
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
*e-mail: yulya.viletska@ukr.net
Received: 19 September 2025; Revised: 13 October 2025;
Accepted: 03 April 2026; Available on-line: 21 April 2026
Endoplasmic reticulum (ER) stress and hypoxia interaction in the progression of glioblastomas and other malignant tumors has not yet been sufficiently studied. Both PSAT1, as the ER stress-responsive phosphoserine aminotransferase, and сyclin D1 are shown to participate in tumor progression and chemoresistance. Therefore, this study aimed to elucidate the effect of endoplasmic reticulum stress on PSAT1 and CCND1 (сyclin D1) genes expression in normal human astrocytes of NHA/TS line, and U87MG glioblastoma cells. Hypoxia was created with the HIF1A prolyl hydroxylase inhibitor dimethyloxalylglycine. Tunicamycin and thapsigargin were used for ER stress induction. PSAT1 and cyclin D1 expression were examined by quantitative real-time RT-PCR. It has been established that hypoxia and tunicamycin had a similar suppressive effect on PSAT1 and CCND1 expression in normal astrocytes, but increased both genes expression in glioblastoma cells. Thapsigargin enhanced PSAT1 expression in both cell lines, but suppressed CCND1 expression in normal astrocytes without any effect on its expression in glioblastoma cells. Hypoxia modified the effect of tunicamycin and thapsigargin when these ER stress inducers were combined with hypoxia, but in different ways in normal and glioblastoma cells. These results indicate that hypoxia and ER stress relationship in the control of the studied genes expression differs in normal and tumor cells.
HSPA5 and DNAJB9 genes expression in glioblastoma cells and normal astrocytes under hypoxia and endoplasmic reticulum stress
O. V. Halkin*, Y. M. Viletska, M. Y. Sliusar, S. V. Danilovskyi,
Y. V. Kulish, O. V. Rudnytska, O. H. Minchenko
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
*e-mail: oleggal2014@gmail.com
Received: 07 October 2025; Revised: 10 December 2025;
Accepted: 30 January 2026; Available on-line: 23 February 2026
Hypoxia and ER stress are obligate factors in tumor growth, however, the interaction between these factors has not been sufficiently studied. Heat shock proteins HSPA5 and DNAJB9 as a key components of the endoplasmic reticulum stress response play an important role in the growth of malignant tumors, including glioblastomas. This study aimed to investigate the interaction between hypoxia and ER stress in controlling HSPA5 and DNAJB9 expression in glioblastoma cells and normal astrocytes. Hypoxia was created with dimethyloxalylglycine, ER stress was induced with tunicamycin and thapsigargin, HSPA5 and DNAJB9 expression was studied by qPCR. It has been established that in astrocytes HSPA5 and DNAJB9 expression was resistant to hypoxia. However, in glioblastoma cells, the expression of these genes under hypoxia was increased. Tunicamycin and thapsigargin enhanced HSPA5 and DNAJB9 expression with a much stronger effect in glioblastoma cells. When these ER stress inducers were combined with hypoxia their effect was modified to a greater extent in normal astrocytes. The obtained results indicate different cell-specific sensitivity of HSPA5 and DNAJB9 expression to hypoxia and ER stress inducers.
Scientific achievements of the Department of Molecular Biology in understanding stress-dependent mechanisms of glioma growth
O. H. Minchenko*, Y. M. Viletska, M. Y. Sliusar, O. O. Khita
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine,
Department of Molecular Biology, Kyiv;
*e-mail: ominchenko@yahoo.com
Received: 09 July 2025; Revised: 25 July 2025;
Accepted: 30 October 2025; Available on-line: 02 December 2025
Since 2005, the Department of Molecular Biology has initiated research aimed at solving key problems in biochemistry and molecular biology, with an emphasis on elucidating the molecular basis of malignant tumor growth and the mechanisms of hypoxic regulation, the role of alternative splicing in the mechanisms of gene expression regulation, as well as the fundamental importance of endoplasmic reticulum stress in maintaining homeostasis and the development of pathological conditions, in particular, the growth of glioblastomas, the most malignant brain tumors that are difficult to treat. It has been shown that the expression of different 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB), key glycolysis regulators, is exacerbated in various malignant tumors and that PFKFB4 is a marker of tumor growth. It has been established that the expression level of PFKFB4 is controlled under hypoxia by a HIF-dependent mechanism, and a HIF-specific sequence has been identified in the promoter, the mutation of which completely removes hypoxic regulation of the PFKFB4 gene. Numerous splice variants of different PFKFB and VEGFA genes have also been identified. It has been established that inhibition of endoplasmic reticulum stress, its ERN1 signaling pathway, reduces the proliferation of glioblastoma cells by changing the expression levels of oncogenes, tumor suppressors, mitochondrial enzymes, as well as insulin and glucocorticoid receptors and their dependent proteins. An important role of ERN1 protein kinase activity in regulating the expression of various genes has been revealed, and its inhibition has been shown to lead to increased invasiveness of glioblastoma cells upon ERN1 knockdown. Attention is focused on studying non-canonical mechanisms of hypoxic gene expression regulation and its dependence on endoplasmic reticulum stress.