MicroRNA-379 inhibits metastasis and epithelial-mesenchymal transition via targeting FAK/AKT signaling in gastric cancer

Int J Oncol. 2017 Sep;51(3):867-876. doi: 10.3892/ijo.2017.4072. Epub 2017 Jul 12.

Abstract

Accumulating evidence demonstrates that aberrant miRNAs contribute to gastric cancer (GC) development and progression. However, the roles of various miRNAs in GC remain to be determined. In the present study, we confirmed that a reduced miR-379 expression was present in GC tissues and cell lines. Our clinical analysis revealed that the downregulated miR-379 expression was significantly correlated with poor prognostic features including lymph node metastasis and advanced TNM stage. Moreover, we confirmed that miR-379 was a novel independent prognostic marker for predicting 5-year survival of GC patients. The ectopic overexpression of miR-379 inhibited cell migration, invasion and EMT progress, while downregulated miR-379 reversed the effect. In addition, miR-379 regulated the focal adhesion kinase (FAK) by directly binding to its 3'-UTR, resulting in suppression of AKT signaling. In clinical samples of GC, miR-379 inversely correlated with FAK, which was upregulated in GC. Alteration of FAK expression or activating AKT signaling at least partially abolished the migration, invasion and EMT progress effects of miR-379 on GC cells. In conclusion, our results indicated that miR-379 functioned as a tumor suppressor gene in regulating the EMT and metastasis of GC via targeting FAK/AKT signaling, and may represent a novel potential therapeutic target and prognostic marker for GC.

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Focal Adhesion Kinase 1 / genetics*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Metastasis
  • Prognosis
  • Proto-Oncogene Proteins c-akt / genetics*
  • Signal Transduction / genetics
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • MIRN379 microRNA, human
  • MicroRNAs
  • Focal Adhesion Kinase 1
  • PTK2 protein, human
  • Proto-Oncogene Proteins c-akt