miR-221 and miR-222 Simultaneously Target RECK and Regulate Growth and Invasion of Gastric Cancer Cells

Med Sci Monit. 2015 Sep 13:21:2718-25. doi: 10.12659/MSM.894324.

Abstract

Background: Although Helicobacter pylori infection is necessary for development of gastric adenocarcinoma (GAC), the underlying mechanism remains poorly defined. This study aimed to explore how miR-221 and miR-222 are dysregulated after H. pylori infection and how these 2 miRNAs are involved in pathological development of gastric cancer.

Material and methods: qRT-PCR analysis was performed to quantify miR-221 and miR-222 expression in patients with H. pylori - induced chronic gastritis, H. pylori-negative healthy controls, and in gastric cancer tissues and the corresponding adjacent normal tissues. Cell models were used to verify the expression profile. Dual luciferase assay was performed to verify putative binding between miR-221 or miR-222 and RECK. A loss-and-gain function study was performed to assess the miR-221/miR-222-RECK axis in gastric cancer cells.

Results: H. pylori infection leads to significantly higher miR-221 and miR-222 expression. MiR-221 and miR-222 can bind the same sequence of RECK 3'UTR, thereby modulating its expression. Through simultaneous regulation over RECK, miR-221 and miR-222 can promote gastric cancer cell growth and invasion.

Conclusions: The miR-221/miR-222-RECK axis might be an important path modulating H. pylori infection-related gastric cancer development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / microbiology
  • Adult
  • Cell Survival
  • Cell Transformation, Neoplastic
  • Female
  • Flow Cytometry
  • GPI-Linked Proteins / metabolism*
  • Gene Expression Regulation, Neoplastic*
  • HEK293 Cells
  • Helicobacter Infections / complications
  • Helicobacter Infections / genetics
  • Helicobacter pylori / metabolism
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Middle Aged
  • Neoplasm Invasiveness
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / microbiology

Substances

  • 3' Untranslated Regions
  • GPI-Linked Proteins
  • MIRN221 microRNA, human
  • MIRN222 microRNA, human
  • MicroRNAs
  • RECK protein, human