MicroRNA-124 upregulation inhibits proliferation and invasion of osteosarcoma cells by targeting sphingosine kinase 1

Hum Cell. 2017 Jan;30(1):30-40. doi: 10.1007/s13577-016-0148-4. Epub 2016 Oct 14.

Abstract

Increasing evidence has confirmed that the dysregulation of microRNAs (miRNAs) contributes to the proliferation and invasion of human cancers. Previous studies have shown that the dysregulation of miR-124 is in numerous cancers. However, the roles of miR-124 in human osteosarcoma (OS) have not been well clarified. Therefore, this study was to investigate the biological functions and molecular mechanisms of miR-124 in OS cell lines, discussing whether it could be a therapeutic biomarker of OS in the future. In this study, our results demonstrated that miR-124 was down-regulated in OS cell lines and tissues. Furthermore, the low level of miR-124 was associated with increased expression of Sphingosine kinase 1 (SPHK1) in OS cells and tissues. Up-regulation of miR-124 significantly inhibited cell proliferation, invasion, and MMP-2 and -9 expressions of OS cells. Bioinformatics analysis predicted that the SPHK1 was a potential target of miR-124. Further study by luciferase reporter assay demonstrated that miR-124 could directly target SPHK1. Overexpression of SPHK1 in OS cells transfected with miR-124 mimic partially reversed the inhibitory of miR-124. In conclusion, miR-124 inhibited cell proliferation and invasion in OS cells by downregulation of SPHK1, and that downregulation of SPHK1 was essential for the miR-124-inhibited cell invasion and in OS cells.

Keywords: Invasion; MicroRNA-124; Osteosarcoma; Proliferation; Sphingosine kinase 1.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Cell Proliferation / physiology
  • Down-Regulation / genetics*
  • Gene Expression / genetics*
  • Gene Expression / physiology
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / physiology*
  • Molecular Targeted Therapy
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Osteosarcoma / genetics*
  • Osteosarcoma / pathology*
  • Osteosarcoma / therapy
  • Phosphotransferases (Alcohol Group Acceptor) / genetics*
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Up-Regulation / genetics*
  • Up-Regulation / physiology*

Substances

  • MIRN124 microRNA, human
  • MicroRNAs
  • Phosphotransferases (Alcohol Group Acceptor)
  • sphingosine kinase