MiR-520b/e Regulates Proliferation and Migration by Simultaneously Targeting EGFR in Gastric Cancer

Cell Physiol Biochem. 2016;40(6):1303-1315. doi: 10.1159/000453183. Epub 2016 Dec 19.

Abstract

Background: MicroRNAs (miRNAs) have been demonstrated to play a crucial role in tumorigenesis. Previous studies have shown that miR-520b/e acts as a tumor suppressor in several tumors. Other studies indicated that epidermal growth factor receptor (EGFR) is highly expressed in many tumors, and involved in the development of tumors, such as cell proliferation, migration, angiogenesis and apoptosis. However, the correlation of miRNAs and EGFR in gastric cancer (GC) has not been adequately investigated. Our aim was to explore the relationship.

Methods: The expression levels of EGFR and miR-520b/e were examined by RT-PCR and Western blot. We also investigated the relationship between EGFR and miR-520b/e in GC cell lines by relevant experiments.

Results: In this study, we found that miR-520b/e inhibits the protein expression of EGFR by directly binding with the 3'-untranslated region (3'-UTR). And it was shown that the down-regulation of miR-520b/e promotes cell proliferation and migration by negative regulation of the EGFR pathway, while over-expression of miR-520b/e inhibits these properties. In addition, the biological function of EGFR in GC cell lines was validated by silencing and over-expression assays respectively.

Conclusions: Taken together, our results demonstrate that miR-520b/e acts as a tumor suppressor by regulating EGFR in GC, and provide a novel marker and insight for the potential therapeutic target of GC.

MeSH terms

  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation
  • Down-Regulation / genetics
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Genes, Reporter
  • Humans
  • Luciferases / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology*
  • Up-Regulation / genetics

Substances

  • MIRN520 microRNA, human
  • MicroRNAs
  • Luciferases
  • EGFR protein, human
  • ErbB Receptors