Overexpression of miR-100 inhibits growth of osteosarcoma through FGFR3

Tumour Biol. 2015 Nov;36(11):8405-11. doi: 10.1007/s13277-015-3581-1. Epub 2015 May 29.

Abstract

Osteosarcoma (OS) is a prevalent, fast growing cancer. Identification of molecular regulation of OS growth may result in development of a novel therapy. Previous studies have highlighted a role of microRNAs (miRNAs) in the regulation of the carcinogenesis of OS, whereas the underlying mechanisms are not completely understood. Moreover, a role of miR-100 in the growth control of OS is not clear. Here we reported significantly higher levels of fibroblast growth factor receptor 3 (FGFR3) and significantly lower levels of miR-100 in the OS specimen, compared to those in the paired normal bone tissues. Bioinformatics analysis and luciferase reporter assay suggest that miR-100 binds to the 3'UTR of FGFR3 mRNA to prevent its translation. To prove it, we modified miR-100 levels in OS cells. We found that overexpression of miR-100 in OS cells decreased FGFR3 protein levels, whereas inhibition of miR-100 increased FGFR3 protein levels, without affecting FGFR3 transcripts. Moreover, overexpression of miR-100 suppressed the OS growth in vitro and in vivo, while inhibition of miR-100 significantly increased OS growth. Taken together, our data demonstrate that miR-100 may inhibit the growth of OS through FGFR3.

Keywords: Fibroblast growth factor receptor 3 (FGFR3); Osteosarcoma (OS); miR-100.

MeSH terms

  • Apoptosis / genetics
  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Osteosarcoma / genetics*
  • Osteosarcoma / pathology
  • RNA, Messenger / biosynthesis
  • Receptor, Fibroblast Growth Factor, Type 3 / biosynthesis*
  • Receptor, Fibroblast Growth Factor, Type 3 / genetics

Substances

  • MIRN100 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • FGFR3 protein, human
  • Receptor, Fibroblast Growth Factor, Type 3