Kubaichuk K. ERN1-dependent regulation of gene expression that control angiogenesis in glioma cell line U87

The main goal of this thesis is to investigate pro-angiogenic and anti-angiogenic factors gene expression in glioma cell lines U87 with ERN1 suppression in conditions of hypoxia and glucose or glutamine deprivation, in order to identify the possible role of these genes in ERN1-mediated angiogenesis and proliferation. It was shown that VEGFA, VEGFB, VEGFC, PDGFC, EREG, HB-EGF, EGFR, PLAU, PLAUR, FGF2, TIMP1, TIMP2, TIMP3, TIMP4, THBS1, THBS2, CTGF, BAI2, SPARC and LUM gene expression, dependents on ERN1 functional activity, and changes in their expression correlates with tumor growth inhibition of glioma cells with ERN1 blockade. We also established that the expression of pro-angiogenic genes was reduced in glioma cells with suppressed function of ERN1. At the same time, the level of gene expression of anti-angiogenic factors was increased in cells with ERN1 blockade. It was also shown that hypoxia, as well as glucose and glutamine deprivation influenced the expression of pro- and anti-angiogenic genes expression. Thus, these results unveil molecular mechanisms of angiogenesis key regulatory factors and interaction mechanisms of ischemia and hypoxia on ERN1 in response to endoplasmic reticulum stress.