miR-370 regulates cell proliferation and migration by targeting EGFR in gastric cancer

Oncol Rep. 2017 Jul;38(1):384-392. doi: 10.3892/or.2017.5660. Epub 2017 May 23.

Abstract

Epidermal growth factor receptor (EGFR) is known to be overexpressed in ~30% of gastric cancer (GC) cases, and may serve as an effective biomarker for predicting the clinical benefit of anti-EGFR therapy. However, the mechanism underlying the regulation of EGFR expression remains unknown. Evidence indicates that post-transcriptional regulation may exist in the process of EGFR expression. In the present study, we aimed to explore whether miR-370 is involved in this process, and how it impacts the biological behaviors of GC cells. In the present study, we first determined the role of EGFR in GC by means of an EGFR overexpression plasmid and siRNAs. Then, the expression levels of EGFR protein and mRNA in GC tissues were analyzed through immunohistochemistry and quantitative RT-PCR (RT-qPCR). Bioinformatics tools and dual-luciferase assay were applied to predict and validate the relevant miRNA targeting EGFR. Finally, human GC MGC-803 cells were selected to explore the effect of miRNA on cell proliferation and migration. We found that suppression of EGFR inhibited the proliferation and migration of GC cells. In addition, the levels of EGFR protein in the GC tissues were ~4 times higher than that in the corresponding paired non-cancerous tissues while the mRNA levels of EGFR were only ~2-fold as high as that in the adjacent non-cancerous tissues. Bioinformatics tools predicted that miRNA-370 was a regulator of EGFR and dual‑luciferase assay validated that miR-370 could directly bind to the 3'-untranslated region (3'-UTR) of EGFR mRNA. Meanwhile, an inverse correlation between miR-370 and EGFR was found in the GC tissues. Overexpression of miR-370 suppressed the proliferation and migration of GC cells, while downregulation of miR-370 promoted proliferation and migration. The present study may provide new information for understanding the molecular mechanism underlying the regulation of EGFR protein expression in GC and may be of important clinical significance to guide targeted therapy.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Down-Regulation
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Signal Transduction / genetics
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • Up-Regulation

Substances

  • 3' Untranslated Regions
  • Biomarkers, Tumor
  • MIRN370 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering
  • EGFR protein, human
  • ErbB Receptors