Hypermethylation-mediated HNF4A silencing by Helicobacter pylori infection drives gastric cancer by disrupting epithelial cell polarity and activating EMT signaling.

ABSTRACT: Helicobacter pylori (Hp.) infection is one of the high-risk factors for gastric carcinogenesis (GC). However, the underlying mechanism remains largely unclear. In this study, we uncover an essential role of Hp. infection in mediating tumor suppressor gene silencing in gastric epithelial cells through promoter DNA hypermethylation. Hepatocyte nuclear factor HNF4A was downregulated in GC and predicted poor survival. The in vitro and in vivo assays together confirmed that HNF4A plays a tumor suppressive role in GC. Single-cell analysis showed that HNF4A was selectively expressed in gastric epithelial cells. Besides, the reduced HNF4A expression in GC was due to promoter DNA hypermethylation. More importantly, we have provided strong evidence that Hp. infection causes HNF4A down-regulation by

SUBMITTER: Li D 

PROVIDER: S-EPMC12500863 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature