The impact of DNA demethylation on the upregulation of the NRN1 and TNFAIP3 genes associated with advanced gastric cancer

AbstractGastric cancer (GC) is the third leading cause of cancer-related death worldwide. Very few therapeutic options are currently available in this neoplasia. The use of 5-Aza-2 ′-deoxycytidine (5-AZAdC) was approved for the treatment of myelodysplastic syndromes, and this drug can treat solid tumours at low doses. Epigenetic manipulation of GC cell lines is a useful tool to better understand gene expression regulatory mechanisms for clinical applications. Therefore, we c ompared the gene expression profile of 5-AZAdC-treated and untreated GC cell lines by a microarray assay. Among the genes identified in this analysis, we selectedNRN1 andTNFAIP3 to be evaluated for gene expression by RT-qPCR and DNA methylation by bisulfite DNA next-generation sequencing in 43 and 52 pairs of GC and adjacent non-neoplastic tissue samples, respectively. We identified 83 candidate genes modulated by DNA methylation in GC cell lines. Increased expression ofNRN1 andTNFAIP3 was associated with advanced tumours (P <  0.05). We showed that increasedNRN1 andTNFAIP3 expression seems to be regulated by DNA demethylation in GC samples: inverse correlations between the mRNA and DNA methylation levels in the promoter ofNRN1 (P <  0.05) and the intron ofTNFAIP3 (P <  0.05) were detected. ReducedNRN1 promoter methylation was associated with III/IV TNM stage tumours (P = 0.03) and the presence ofHelicobacter pylori infection (P = 0.02). The identification of demethylated activat...
Source: Journal of Molecular Medicine - Category: Molecular Biology Source Type: research