title: INHIBITION OF ERN1 SIGNALING ENZYME AFFECTS HYPOXIC REGULATION OF THE EXPRESSION OF E2F8, EPAS1, HOXC6, ATF3, TBX3 AND FOXF1 GENES IN U87 GLIOMA CELLS.
abstract: Hypoxia as well as the endoplasmic reticulum stress are important factors of malignant tumor growth and control of the expression of genes, which regulate numerous metabolic processes and cell proliferation. Furthermore, blockade of ERN1 (endoplasmic reticulum to nucleus 1) suppresses cell proliferation and tumor growth. We studied the effect of hypoxia on the expression of genes encoding the transcription factors such as E2F8 (E2F transcription factor 8), EPAS1 (endothelial PAS domain protein 1), TBX3 (T-box 3), ATF3 (activating transcription factor 3), FOXF1 (forkhead box F), and HOXC6 (homeobox C6) in U87 glioma cells with and without ERN1 signaling enzyme function. We have established that hypoxia enhances the expression of HOXC6, E2F8, ATF3, and EPAS1 genes but does not change TBX3 and FOXF1 gene expression in glioma cells with ERNI function. At the same time, the expression level of all studied genes is strongly decreased, except for TBX3 gene, in glioma cells without ERN1 function. Moreover, the inhibition of ERN1 signaling enzyme function significantly modifies the effect of hypoxia on the expression of these transcription factor genes. removes or introduces this regulation as well as changes a direction or magnitude of hypoxic regulation. Present study demonstrates that fine-tuning of the expression of proliferation related genes depends upon hypoxia and ERN1-mediated endoplasmic reticulum stress signaling and correlates with slower proliferation rate of glioma cells without ERN1 function.
authors.forename: O H
authors.initials: OH
authors.lastname: Minchenko
authors.forename: D O
authors.initials: DO
authors.lastname: Tsymbal
authors.forename: D O
authors.initials: DO
authors.lastname: Minchenko
authors.forename: O V
authors.initials: OV
authors.lastname: Kovalevska
authors.forename: L L
authors.initials: LL
authors.lastname: Karbovskyi
authors.forename: A
authors.initials: A
authors.lastname: Bikfalvi
mesh_terms: D051700:Activating Transcription Factor 3 / Q000235:genetics / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D015687:Cell Hypoxia / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D059865:Endoplasmic Reticulum Stress / Q000235:genetics; D004722:Endoribonucleases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010100:Oxygen / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051700:Activating Transcription Factor 3; D051792:Basic Helix-Loop-Helix Proteins; D004722:Endoribonucleases; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D010100:Oxygen; D017346:Protein Serine-Threonine Kinases; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D020825:T-Box Domain Proteins; D000099162:Endothelial PAS Domain-Containing Protein 1; C490449:ATF3 protein, human; C504723:E2F8 protein, human; C098521:FOXF1 protein, human; C094289:HOXC6 protein, human; C106884:TBX3 protein, human; C528229:ERN1 protein, human