MicroRNA-126 regulates migration and invasion of gastric cancer by targeting CADM1

Int J Clin Exp Pathol. 2015 Aug 1;8(8):8869-80. eCollection 2015.

Abstract

Objective: The aberrant expression of microRNAs has been demonstrated to play a crucial role in the initiation and progression of gastric cancer (GC). We here aimed to investigate the mechanism of microRNAs in the regulation of GC pathogenesis.

Methods: Transwell chambers (8-μM pore size; Costar) were used in the in vitro migration and in vision assay. Dual luciferase reporter gene construct and dual luciferase reporter assay to identify the target of miR-126. CADM1 expression was evaluated by immunohistochemical staining. The clinical manifestations, treatments and survival were collected for statistical analysis.

Results: Inhibition of miR-126 effectively reduced migration and invasion of gastric cancer cell lines. Bioinformatics and luciferase reporter assay revealed that miR-126 specifically targeted the 3'UTR of cell adhesion molecule 1 (CADM1) and regulated its expression. Down-regulation of CADM1 enhanced migration and invasion of GC cell lines. Furthermore, in tumor tissues obtained from gastric cancer patients, the expression of miR-126 was negatively correlated with CADM1 and the high expression of miR-126 combined with low expression of CADM1 might serve as a risk factor for stage1 gastric cancer patients.

Conclusions: Our study showed that miR-126, by down-regulation CADM1, enhances migration and invasion in GC cells.

Keywords: Gastric cancer (GC); cell adhesion molecule 1 (CADM1); invasion; microRNA-126.

MeSH terms

  • Animals
  • Apoptosis
  • Blotting, Western
  • Cell Adhesion Molecule-1
  • Cell Adhesion Molecules / biosynthesis*
  • Cell Adhesion Molecules / genetics
  • Cell Line, Tumor
  • Cell Movement* / genetics
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic / genetics*
  • Heterografts
  • Humans
  • Immunoglobulins / biosynthesis*
  • Immunoglobulins / genetics
  • Immunohistochemistry
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Polymerase Chain Reaction
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology*

Substances

  • CADM1 protein, human
  • Cell Adhesion Molecule-1
  • Cell Adhesion Molecules
  • Immunoglobulins
  • MIRN126 microRNA, human
  • MicroRNAs