Tumor suppressor microRNA-31 inhibits gastric carcinogenesis by targeting Smad4 and SGPP2

Cancer Gene Ther. 2015 Dec;22(12):564-72. doi: 10.1038/cgt.2015.41. Epub 2015 Oct 23.

Abstract

To investigate the function of microRNA-31 (miR-31) in the pathogenesis of gastric cancer (GC) and to explore the possible mechanisms involved in it. A quantitative real-time reverse transcription-PCR (RT-PCR) analysis was performed to evaluate miR-31 expression in GC cell lines. After transfecting GC cells with miR-31 precursors, Alamar blue and apoptosis assays were used to measure the respective proliferation and apoptosis rates. SGPP2 and Smad4 expression were determined by real-time RT-PCR and western blot assays after miR-31 transfection. Animal assay was used to further investigate miR-31 in the pathogenesis of GC. miR-31 was significantly reduced in GC tissues and GC cell lines, and that the reduced miR-31 was associated with distant metastasis and GC clinical pathological stages, miR-31 was lower at stages III/IV than that at stage II. SGPP2 and Smad4 were proven to be the direct target of miR-31. SGPP2 and Smad4 at mRNA and protein levels were negatively correlated with miR-31 in human GC tissues and cancer cell lines. Increased miR-31 significantly repressed SGPP2 and Smad4 at transcriptional and translational levels. Functional studies showed that increasing miR-31 inhibited GC cell proliferation, promoted apoptosis and attenuated cell migration, which were also linked to downregulation of STAT3. In vivo, miR-31 inhibited GC cell growth in tumor-bearing mice. This study has revealed miR-31 as a tumor suppressor and has identified SGPP2 and Smad4 as novel targets of miR-31, linking to STAT3 for regulating cancer cell proliferation, apoptosis and migration in GC. Therefore, miR-31 could be a useful biomarker for monitoring GC development and progression, and also could have a therapeutic potential by targeting SGPP2, Smad4 and STAT3 for GC therapy.

Publication types

  • Retracted Publication

MeSH terms

  • Animals
  • Apoptosis
  • Carcinogenesis*
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • Humans
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Mice
  • MicroRNAs / genetics*
  • Phosphoric Monoester Hydrolases / genetics*
  • Phosphoric Monoester Hydrolases / metabolism
  • Smad4 Protein / genetics*
  • Smad4 Protein / metabolism
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / physiopathology
  • Transfection
  • Transgenes

Substances

  • MIRN31 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • Mirn31 microRNA, mouse
  • Smad4 Protein
  • SGPP2 protein, human
  • Phosphoric Monoester Hydrolases