The multifaceted role of endoplasmic reticulum stress in the regulation of gene expression in normal astrocytes and glioblastoma cells

Aim. To determine the role of the endoplasmic reticulum (ER) in regulating gene expression in normal astrocytes and glioblastoma cells under the application of carbon nanoparticles as anti-tumor agents and inhibition of ERN1 (endoplasmic reticulum to nucleus signaling 1). Methods. Aqueous dispersions of graphene oxide (GO) and aqueous suspensions of single-walled carbon nanotubes (SWCNTs) were used to study the impact of carbon nanoparticles. Experiments were conducted on regular human astrocytes line NHA/TS and U87MG glioblastoma cells. Two sublines of ERN1 knockdown cells were applied to determine the role of ERN1 in the control of gene expression. Quantitative RT-PCR detected the expression level of mRNA and microRNA. Results. It was shown that GO and SWCNTs affect the expression of numerous regulatory genes in both normal human astrocytes and glioblastoma cells, but the effect was less pronounced in glioblastoma cells than in normal astrocytes and preferentially mediated by ERN1. The expression of serine biosynthesis genes is controlled by ERN1 protein kinase or endoribonuclease activity. Furthermore, the inhibition of functional activity of ERN1 modifies the effects of hypoxia on gene expression. Conclusions. Thus, these results demonstrated that ER stress plays an essential role in controlling the expression of various regulatory genes in glioblastoma cells and that normal astrocytes are more sensitive to the effect of carbon nanoparticles than glioblastoma cells.