MicroRNA-196a/-196b promote cell metastasis via negative regulation of radixin in human gastric cancer

Cancer Lett. 2014 Sep 1;351(2):222-31. doi: 10.1016/j.canlet.2014.06.004. Epub 2014 Jun 13.

Abstract

MicroRNAs (miRNAs) play an important role to contribute carcinogenesis. The aim of the current study was to identify useful biomarkers from miRNAs. Differential miRNA profiles were analyzed using the miRNA qRT-PCR-based assay. Two of the most upregulated miRNAs were selected and validated. The miR-196a/-196b levels were significantly increased in gastric cancer (GC) tissues (n=109). Overexpression of miR-196a/-196b was significantly associated with tumor progression and poorer 5-year survival outcomes. Overexpression of miR-196a/-196b enhances GC cell migration and invasion. Further, radixin was identified as a target gene of miR-196a/-196b. Elevated miR-196a/-196b expression in GC cells led to reduced radixin protein levels and vice versa. Notably, an inverse correlation between miR-196a/-196b and radixin mRNA and protein expression was observed in GC tissues with in situ hybridization and immunohistochemistry analyses. Together, miR-196a/-196b inhibitory oligonucleotides or overexpression of the radixin may thus have therapeutic potential in suppressing GC metastasis.

Keywords: Gastric cancer; Metastasis; Prognosis; Radixin; miR-196a/-196b.

MeSH terms

  • Aged
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cytoskeletal Proteins / biosynthesis
  • Cytoskeletal Proteins / genetics*
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, Tumor Suppressor
  • Humans
  • Immunohistochemistry
  • Male
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / genetics*
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prognosis
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Transfection
  • Tumor Cells, Cultured
  • Up-Regulation

Substances

  • Cytoskeletal Proteins
  • MIRN196 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • radixin