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It was shown previously that inhibition of erN1 (endoplasmic reticulum to nucleus signaling 1) pathway, a central mediator of the unfolded protein response, leads to suppression of tumor growth through downregulation of key pro-proliferative and up-regulation of tumor suppressor factors and modifies the sensitivity of these genes to glucose and glutamine deprivation. However, the executive mechanisms of erN1 mediated control of glioma cell proliferation are not yet known. The goal of this study was to estimate the effect of glucose and glutamine deprivations on expression of cancer related genes in glioma U87 cells at erN1 signaling inhibition for evaluation of their possible significance in ERN1 mediated control of glioma cell proliferation. We studied the effect of glucose and glutamine deprivations on the expression level of cancer related genes encoding TMED10 (transmembrane p24 trafficking protein 10), MYL9 (myosin, light chain 9, regulatory), SPOck1 (sparc/osteonectin, cwcv and kazal-like domains proteoglycan 1), cUl4a (cullin 4a), and cUl4B in U87 glioma control cells and cells with erN1 knockdown. It was shown that at glucose deprivation, the expression level of MYL9, SPOCK1 and CUL4B genes was significantly up-regulated in control glioma cells. ERN1 knockdown modified the sensitivity to glucose deprivation of all studied genes except TMED10 gene. At glutamine deprivation, the expression of Myl9, cUl4a and cUl4B genes was shown to be up-regulated in control glioma cells. the sensitivity of Myl9, tMeD10 and cUl4B gene expression to glutamine deprivation in glioma cells with ERN1 knockdown was significantly modified, while CUL4A and SPOCK1 gene expression did not respond to erN1 inhibition. the present study demonstrates that glucose and glutamine deprivation affected the expression of the most studied genes in a specific manner and that inhibition of ERN1 signaling preferentially modified their expression at glucose and glutamine deprivation.

ERN1 dependent regulation of TMED10, MYL9, SPOCK1, CUL4A and CUL4B genes expression at glucose and glutamine deprivations in U87 glioma cells