Abstract
BackgroundRecent observations indicate a decreased cancer risk in patients with Alzheimer’s disease (AD). AD is a severe neurodegenerative disorder characterized by progressive cognitive decline. The 8q24 region has been shown to be involved in AD aetiology. We aimed to identify and explore the potential oncogenes or antioncogenes on chromosome 8q24.MethodsWe compared expression of genes on Chromosome 8q24 in 32 pairs of samples from The Cancer Genome Atlas (TCGA) database. We conducted bioinformatics analysis of the commonly used gastric cancer databases and performed clinical verification of gastric cancer samples, combined with assessment of biological function both in vitro and in vivo to determine the relationship between upregulated expression of GRINA and gastric cancer progression. We also explored the molecular mechanism of GRINA upregulation and its function in gastric cancer development and progression.ResultsThe expression of GRINA in cancer tissues was significantly higher than that in normal tissues. GRINA indicated poor prognosis in gastric cancer. GRINA promoted the proliferation, migration and invasion capacity of gastric cancer cells. GRINA was transcriptionally mediated by c-Myc and promotes cell cycle transition. GRINA knockdown decreased PI3K/Akt/mTOR signaling and glycolytic metabolism in gastric cancer cells. The apoptosis rate was significantly increased in gastric cancer cell lines after knockdown of GRINA. The expression of pro-apoptotic protein Bax was significantly upregulated, whereas the anti-apoptotic protein Bcl-2 was significantly downregulated in GRINA silenced cells.ConclusionsHuman gastric cancers have increased levels of GRINA, which promotes growth of gastric cancer and inhibits tumor cells apoptosis.
Highlights
Recent observations indicate a decreased cancer risk in patients with Alzheimer’s disease (AD)
GRINA expression is elevated in gastric cancer tissues compared with that in normal tissues Comparing gene expression in 32 pairs of cancerous and noncancerous tissues from patients with gastric cancer in The Cancer Genome Atlas (TCGA) database revealed 36 dysregulated genes on chromosome 8q24 (Fig. 1a, Additional file 5: Figure S1A), 5 of which were downregulated and 31 upregulated in gastric cancer tissues (Additional file 6: Table S5, Additional file 7: Table S6)
In samples from TCGA database and Gene Expression Omnibus (GEO) database, GRINA expression was found to be significantly increased in gastric cancer samples compared with that in normal samples (Figs 1b-1d)
Summary
Recent observations indicate a decreased cancer risk in patients with Alzheimer’s disease (AD). A significant number of patients present with advanced disease, leading to poor survival. The prognosis for advanced gastric cancer is poor; less than 10–15% of patients with metastases live for more than 2 years [2]. Copy number alteration (CNA) on Chromosome 8q24.3 is the main mechanism underlying tumorigenesis [8]. Glutamate Receptor, Ionotropic, N-Methyl D-Aspartate-Associated Protein 1 (GRINA) is located at chromosome 8q24.3 and belongs to the N-Methyl D-Aspartate (NMDA) receptors which are closely associated with tumour progression according to some studies [9]. Knockdown of NR2A, which belongs to NMDA receptor family, induced cell cycle to arrest in the G1 phase and suppressed the proliferation of MKN45 cells [12]
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