miR-7 inhibits the invasion and metastasis of gastric cancer cells by suppressing epidermal growth factor receptor expression

Oncol Rep. 2014 Apr;31(4):1715-22. doi: 10.3892/or.2014.3052. Epub 2014 Feb 24.

Abstract

The present study profiled differentially expressed microRNAs (miRs) in gastric cancer cell lines and then investigated miR-7 expression in gastric cancer tissue specimens and the effects of miR-7 on the growth, invasion and metastasis of gastric cancer cells and the underlying molecular events. A microRNA microarray was used to profile differentially expressed miRNAs in human gastric cancer cell lines relative to a normal stomach mucosal epithelial cell line. The miRNA miR-7 was selected for further investigation, which included real-time reverse-transcription PCR (qRT-PCR) analysis of miR-7 levels in different gastric cancer cell lines and tissues and distant non-tumor tissues from patient resections. Cell counting kit-8 (CCK-8), Transwell migration and invasion, and western blot assays were performed to assess tumor cell viability, invasion and gene expression, respectively, after miR-7 transfection. The miRNA microarray profiling revealed 14 upregulated miRNAs (including miR-21, miR-26b and miR-30b) and 19 downregulated miRNAs (including let-7i, miR-7 and miR-622) between gastric cancer and normal cell lines. The qRT-PCR analysis confirmed that reduced miR-7 expression occurred more frequently in poorly and moderately differentiated gastric cancer MGC-803, MKN-45 and SGC-7901 cell lines than in the well-differentiated gastric cancer NCI-N87 cell line, which was consistent with the results for gastric cancer tissues. Expression of miR-7 was downregulated in 86.9% (20/23) of the gastric cancer tissues compared with that in the distant non-tumor tissues. Restoration of miR-7 expression significantly inhibited tumor cell viability, invasiveness and migration when compared with the control cells. Luciferase assay confirmed the epidermal growth factor receptor (EGFR) as a target gene of mR-7, and expression of miR-7 significantly suppressed EGFR expression at both the mRNA and protein levels. The data from the present study demonstrated that reduced miR-7 expression contributes to gastric cancer development and progression. Further study will investigate miR-7 in the regulation of EGFR expression in vitro and in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Survival
  • ErbB Receptors / biosynthesis*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Oligonucleotide Array Sequence Analysis
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Transfection

Substances

  • MIRN7 microRNA, human
  • MicroRNAs
  • EGFR protein, human
  • ErbB Receptors