THE EFFECT OF HELICOBACTER PYLORI ON THE PATTERN OF METHYLATION OF GENE

Background and Aim:Helicobacter pylori affects about half of the world s population and can cause various diseases, including gastric cancer, due to its pathogens. One of the causes of cancer occurrence is epigenetic changes, including increased methylation of genes. In this study, we study the ability of this bacteria in changing the pattern of methylation of promoter gene HS3ST2. HS3ST2 is one of the major enzymes in biosynthesis and the final edition of heparan sulfate.Methods:H. pylori was prepared from the hospital sources. After preparation, the bacteria were co-cultured for 24, 48 and 72 hours with AGS and MKN-45 cell lines (previously non-methylated) with ratios of 1 cell / 50 HP and 1 cell / 100 HP. Methylation-Specific Quantitative-PCR (MS-qPCR) was performed after extraction and sulfite removal of the genomic DNAs of the cells and the amount of HS3ST2 gene methylation was calculated.Results:H. pylori was able to significantly increase the amount of methylation of the islands rich in CpG dinucleotides of HS3ST2 promoter gene in AGS cell line from 10 to 33% and in MKN-45 cell line from 4 to 14%. Increasing the methylation of this gene has a direct relationship with the time of adjoining bacteria with the cell and the concentration of the bacteria in the medium.Conclusion:Probably H. pylori, through its pathogens, disrupts the activity of DNMTs and SAM, resulting in increased DNA methylation of the gastric cells. This causes changes or disruption of the normal activity of the cell and will result in the occurrence of cancer.

کلیدواژه ها:

Helicobacter pylori ، HS2ST2 ، Gastric cancer ، DNA methylation ، MS-qPCR