MicroRNA-137 is downregulated in human osteosarcoma and regulates cell proliferation and migration through targeting FXYD6

J Drug Target. 2016;24(2):102-10. doi: 10.3109/1061186X.2015.1057149.

Abstract

Background: In this work, we investigated the functional role of microRNA 137 (miR-137) in regulating osteosarcoma both in vitro and in vivo.

Methods: Quantitative RT-PCR was used to examine the gene expressions of miR-137 in osteosarcoma cell lines and osteosarcoma tumors. 143B and Saos-2 cells were infected with lentivirus expressing miR-137 mimics (miR-137-mimic) to ectopically upregulate miR-137. In vitro cancer proliferation and migration were examined by MTT assay and transwell assay, respectively. Viral infected Saos-2 cells were also subcutaneously inoculated into null mice to evaluate the effect of miR-137 upregulation on in vivo tumor growth. The interaction between miR-137 and its downstream target, FXYD6, was evaluated by dual-luciferase reporter assay and quantitative real-time PCR. FXYD6 was then subsequently upregulated in osteosarcoma cells to evaluate its effect on miR-137 regulation in osteosarcoma.

Results: We found that miR-137 was significantly downregulated in both osteosarcoma cell lines and osteosarcoma tumors. Lentiviral infection of miR-137-mimic upregulated miR-137 gene expression, reduced in vitro proliferation and migration and inhibited in vivo osteosarcoma tumor growth. FXYD6 was verified to be directly interacting with miR-137, and its subsequent upregulation reversed the inhibitory effect of miR-137 upregulation in osteosarcoma.

Conclusion: We revealed novel functional role of miR-137 in osteosarcoma regulation, likely through FXYD6 binding.

MeSH terms

  • Animals
  • Bone Neoplasms / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Down-Regulation / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • HEK293 Cells
  • Humans
  • Ion Channels / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Osteosarcoma / genetics*
  • Up-Regulation / genetics

Substances

  • FXYD6 protein, human
  • Ion Channels
  • MIRN137 microRNA, human
  • MicroRNAs