Endoplasmic reticulum stress-dependent regulation of the expression of serine hydroxymethyltransferase 2 in glioblastoma cells.

Serine hydroxymethyltransferase (SHMT2) plays a multifunctional role in mitochondria (folate-dependent tRNA methylation, translation, and thymidylate synthesis). The endoplasmic reticulum stress, hypoxia, and glucose and glutamine supply are significant factors of malignant tumor growth including glioblastoma. Previous studies have shown that the knockdown of the endoplasmic reticulum to nucleus signaling 1 (ERN1) pathway of endoplasmic reticulum stress strongly suppressed glioblastoma cell proliferation and modified the sensitivity of these cells to hypoxia and glucose or glutamine deprivations.

Hypoxia controls the expression of genes responsible for serine synthesis in U87MG cells on ERN1-dependent manner.

Serine synthesis as well as endoplasmic reticulum stress and hypoxia are important factors of malignant tumor growth including glioblastoma. Previous studies have shown that the knockdown of ERN1 (endoplasmic reticulum to nucleus signaling) significantly suppressed the glioblastoma cell proliferation and modified the hypoxia regulation. The present study is aimed to investigate the impact of hypoxia on the expression of (phosphoglycerate dehydrogenase), (phosphoserine aminotransferase 1), (phosphoserine phosphatase), (activating transcription factor 4), and (serine hydroxymethyltransferase 1) in U87MG glioblastoma cells in relation to knockdown of ERN1 with the intent to reveal the role of ERN1 signaling pathway on the endoplasmic reticulum stress-dependent regulation of expression of these genes.

The impact of glutamine deprivation on the expression of MEIS3, SPAG4, LHX1, LHX2, and LHX6 genes in ERN1 knockdown U87 glioma cells.

The aim of the current study was to investigate the expression of genes encoded homeobox proteins such as MEIS3 (Meis homeobox 3), SPAG4 (sperm associated antigen 4), LHX1 (LIM homeobox 1), LHX2, and LHX6 in U87 glioma cells in response to glutamine deprivation in control glioma cells and cells with knockdown of ERN1 (endoplasmic reticulum to nucleus signaling 1), the major pathway of the endoplasmic reticulum stress signaling, for evaluation of a possible dependence on the expression of these important regulatory genes from glutamine supply and ERN1 signaling. The expression level of , , , , and genes was studied by real-time quantitative polymerase chain reaction in control U87 glioma cells (transfected by vector) and cells with ERN1 knockdown after exposure to glutamine deprivation. It was shown that the expression level of and genes was up-regulated in control glioma cells treated by glutamine deprivation.