Helicobacter pylori infection promotes methylation of WWOX gene in human gastric cancer

WW domain-containing oxidoreductase (WWOX), a tumor suppressor gene, was reported to be downregulated in gastric cancer and other tumors. However, the mechanism by which WWOX is inactivated remains unclear. In our study, methylation status of WWOX was determined by MSP and sequencing. Our results showed that WWOX hypermethylation was frequently detected in gastric cancer, and also significantly correlated with Helicobacter pylori (H. pylori) infection. Promoter methylation of WWOX was induced in BCG823 and AGS cells co-cultured with H. pylori. Finally, we found that expression of DNMT1 and DNMT3A were enhanced when cells were co-cultured with H. pylori. Our study indicated that H. pylori infection promoted methylation of WWOX gene in gastric cancer.

► WWOX was hypermethylated in gastric cancer.
► WWOX hypermethylation was correlated with Helicobacter pylori infection.
► H. pylori infection increases the expression of DNMT1 and DNMT3A.