miR-16 inhibits cell proliferation by targeting IGF1R and the Raf1-MEK1/2-ERK1/2 pathway in osteosarcoma

FEBS Lett. 2013 May 2;587(9):1366-72. doi: 10.1016/j.febslet.2013.03.007. Epub 2013 Mar 15.

Abstract

Several miRNAs have been implicated in the development and progression of osteosarcoma (OS). In this study, we found that miR-16 is downregulated in OS cell lines and tissues. Overexpression of miR-16 suppresses OS cell proliferation and tumor growth in nude mice. Furthermore, we confirmed that IGF1R is a direct target of miR-16. Mechanistic investigation revealed that miR-16 overexpression inhibits the Raf1-MEK1/2-ERK1/2 pathway. In clinical specimens, IGF1R levels inversely correlate with miR-16 expression. Our results provide significant clues regarding the role of miR-16 as a tumor suppressor by targeting IGF1R in OS.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation / genetics
  • Humans
  • MAP Kinase Kinase 1 / metabolism
  • MAP Kinase Kinase 2 / metabolism
  • MAP Kinase Signaling System / genetics*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Osteosarcoma / genetics
  • Osteosarcoma / pathology*
  • Proto-Oncogene Proteins c-raf / metabolism
  • Receptor, IGF Type 1 / genetics*

Substances

  • MIRN16 microRNA, human
  • MicroRNAs
  • MAP2K2 protein, human
  • Receptor, IGF Type 1
  • Proto-Oncogene Proteins c-raf
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • MAP Kinase Kinase 1
  • MAP Kinase Kinase 2