Helicobacter pylori Is Associated with miR-133a Expression through Promoter Methylation in Gastric Carcinogenesis

ABSTRACT

BACKGROUND/AIMS: To investigate whether Helicobacter pylori eradication can reverse epigenetic silencing of microRNAs (miRNAs) which are associated with H. pylori-induced gastric carcinogenesis. METHODS: We examined expression and promoter methylation of miR-34b/c, miR-133a, let-7a, and let-7i in gastric cancer cell line, before/after demethylation. Among them, epigenetically controlled miRNAs were identified. Their expression and promoter methylation was examined in human tissues of H. pylori-positive gastric cancer (T), H. pylori-positive gastritis (H), and H. pylori-negative controls (C). We also compared changes of miRNA expression and promoter methylation in H. pylori-positive patients who were endoscopically treated for early gastric cancer, between baseline and 1 year later according to eradication status. RESULTS: In gastric cancer cell line, miR-34b/c and miR-133a showed epigenetic silencing. In human tissues, miR-34b/c and miR-133a showed serial increase of promoter methylation in order of C, H, and T (all, p < 0.01), and the miR-133a expression showed serial decrease (C vs H, p=0.02; H vs T, p=0.01; C vs T, p < 0.01) while miR-34b and miR-34c expressions did not. H. pylori eradication induced decrease of methylation (p < 0.01) and increase of miR-133a expression (p=0.03), compared with noneradication group. CONCLUSIONS: This result suggests H. pylori eradication could reverse methylation-silencing of miR-133a which is involved in H. pylori-induced gastric carcinogenesis.