The role of EBV infected Gastric cancer in increasing miR-124 promoter methylation and EZH2 gene expression

The tumor suppressor microRNAs, miR-21, miR-124, and miR-494, participate in the controlling several cellular processes. In our study, target miRs methylation levels in the 304 pairs of GC (as non-tumor tissues) were assessed. To detect EBV and H. Pylori DNA in GC tissues, a commercial real time PCR EBV and H. Pylori kit was used. Following the discovery of hyper-methylation of the miR-124 gene promoter, its expression level was assessed by qPCR. miR-124 is identified as the EZH2 target by bioinformatics analysis. The association between EZH2 and miR-124 EZH2 was confirmed using qPCR. EBV and H. Pylori DNA were detected in 9.5% and 15.1% of GC patients of the 304 subjects. Among the miRs studied, miR-124 methylation level were significantly difference in EBV-infected GC patients in comparison to total GC patients, H. pylori infected GC patients, GC patients without EBV and H. pylori infection, and non-tumor tissue. The analysis of bioinformatics and qPCR assays indicated an inverse relationship between the levels of expression of EZH2 and miR-124 in EBV-infected GC patients. According to our data, miR-124 gene promoter was hyper-methylated, and its expression was significantly reduced in EBV-infected GC tissues. It is possible that miR-124 plays a role in the development of EBV-infected GC by targeting EZH2, given its capability to bind to the 3'-UTR of the EZH2 gene.