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: 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.

Keywords: endoplasmic reticulum stress, ERN1, gene expression, glioblastoma cells, hypoxia