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

Joo Hyun Lim1,2, Sang Gyun Kim2, Ji Min Choi1

  • 1Department of Internal Medicine and Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea.

Gut and Liver
|September 28, 2017
PubMed
Abstract

Insights

Helicobacter pylori eradication can reverse epigenetic silencing of miR-133a, a microRNA (miRNA) involved in gastric cancer. This finding suggests a potential therapeutic strategy for H. pylori-associated gastric carcinogenesis.

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Oncology

Background:

  • Helicobacter pylori infection is a major risk factor for gastric cancer.
  • Epigenetic silencing of microRNAs (miRNAs) plays a role in H. pylori-induced gastric carcinogenesis.
  • Specific miRNAs like miR-133a are implicated in this process.

Purpose of the Study:

  • To investigate if H. pylori eradication can reverse the epigenetic silencing of specific miRNAs.
  • To determine the role of miR-133a in H. pylori-associated gastric carcinogenesis.
  • To assess the impact of H. pylori eradication on miRNA expression and methylation.

Main Methods:

  • Examined expression and promoter methylation of miR-34b/c, miR-133a, let-7a, and let-7i in gastric cancer cell lines and human tissues.
  • Assessed miRNA changes in H. pylori-positive patients before and after treatment, comparing eradication and non-eradication groups.
  • Utilized demethylation in cell lines to identify epigenetically controlled miRNAs.

Main Results:

  • miR-133a and miR-34b/c showed epigenetic silencing in gastric cancer cell lines.
  • Promoter methylation of miR-34b/c and miR-133a increased progressively from control to gastritis to cancer tissues.
  • H. pylori eradication led to decreased miR-133a promoter methylation and increased expression.

Conclusions:

  • H. pylori eradication can reverse the methylation-based silencing of miR-133a.
  • miR-133a is involved in H. pylori-induced gastric carcinogenesis.
  • Targeting epigenetic modifications may offer a therapeutic approach for H. pylori-related gastric cancer.

Related Concept Videos

Pathophysiology of Peptic Ulcer Disease: Mucosal Defense Factors01:24

Pathophysiology of Peptic Ulcer Disease: Mucosal Defense Factors

Peptic ulcer disease, commonly called PUD, represents a multifaceted condition characterized by disruptions in the lining of the gastrointestinal (GI)  tract. Central to the protection of the gastrointestinal lining is the mucosal-bicarbonate barrier. This physiological defense mechanism is a formidable shield against the corrosive effects of gastric acid and pepsin secretion in the stomach. Its role is pivotal in maintaining the structural integrity of the stomach's inner lining.
1.3K
Gastritis-II: Pathophysiology01:17

Gastritis-II: Pathophysiology

Gastritis is marked by disruption of the mucosal barrier that usually protects the stomach tissue from digestive juices and manifests in acute and chronic forms.
In acute gastritis, the gastric mucosa becomes swollen and red and undergoes superficial erosion. Superficial ulceration may lead to bleeding.
In chronic gastritis, persistent or repeated insults lead to chronic inflammatory changes and, eventually, thinning or atrophy of the gastric tissue.
Gastritis can stem from various causes, each...
1.4K
Peptic Ulcer Disease I: Introduction01:30

Peptic Ulcer Disease I: Introduction

Peptic Ulcer Disease (PUD) is characterized by mucosal excavation in the esophagus, stomach, pylorus, or duodenum. It can manifest as acute or chronic based on the extent and duration of mucosal involvement.
An acute ulcer, marked by superficial erosion and minimal inflammation, swiftly resolves upon identifying and addressing the underlying cause. In contrast, a chronic ulcer persists, potentially eroding through the muscular wall and forming fibrous tissue.
Peptic ulcers can also be...
917
Treating Helicobacter pylori in Peptic Ulcers: Antimicrobial Therapy01:16

Treating Helicobacter pylori in Peptic Ulcers: Antimicrobial Therapy

Helicobacter pylori, a resilient gram-negative bacterium, can thrive in the stomach's harsh, acidic environment. Infection with H. pylori leads to a cascade of events within the stomach lining. One of the critical disruptions caused by this bacterium is the interference with somatostatin production, a hormone responsible for regulating acid secretion. This interference tips the balance, escalating acid secretion and diminishing bicarbonate levels. This imbalance compromises the defensive...
1.5K
Pathophysiology of Peptic Ulcer Disease: Injurious Factors01:22

Pathophysiology of Peptic Ulcer Disease: Injurious Factors

Peptic ulcers are sores on the stomach's inner lining and the upper small intestine, which are the result of disruptions in the mucosal layer that houses parietal cells which produce gastric acid, and chief cells which secrete pepsinogen.
In the antrum region, G cells secrete the gastrin hormone that binds to gastrin-cholecystokinin-B (CCK2) receptors on parietal and enterochromaffin-like (ECL) cells in the fundic glands. Simultaneously, the vagus nerve releases acetylcholine, which binds...
1.3K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
24.4K