Gut Liver.  2018 Jan;12(1):58-66. 10.5009/gnl17263.

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

Affiliations
  • 1Department of Internal Medicine and Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea.
  • 2Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea. harley1333@hanmail.net
  • 3Division of Gastroenterology, Department of Internal Medicine and Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.

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.

Keyword

Helicobacter pylori; Methylation; MicroRNAs; Stomach neoplasms

MeSH Terms

Carcinogenesis*
Cell Line
Epigenomics
Gastritis
Helicobacter pylori*
Helicobacter*
Humans
Methylation*
MicroRNAs
Stomach Neoplasms
MicroRNAs
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