miR-15b Inhibits the Progression of Glioblastoma Cells Through Targeting Insulin-like Growth Factor Receptor 1

Horm Cancer. 2017 Feb;8(1):49-57. doi: 10.1007/s12672-016-0276-z. Epub 2016 Nov 28.

Abstract

The microRNAs (miRNAs) have been suggested as a tumor suppressor in recent years. miR-15b was reported to exert an anti-oncogenic role in the proliferation, migration, and invasion of diverse tumor cells. However, the mechanisms underlying miR-15b-mediated biology of glioblastoma are still unclear. In the present study, the expression of miR-15b was down-regulated in glioblastoma tumor tissues and U87 and U251 cells, but insulin-like growth factor receptor 1 (IGF1R) expression became up-regulated in these tumor tissues and cells (all p < 0.001). Furthermore, IGF1R expression was inversely associated with miR-15b expression. Notably, patients with lower miR-15b expression have a much shorter survival period compared with high expression (log-rank test p = 0.045). In vitro data demonstrated that miR-15b mimics inhibited the proliferation, cell cycle arrest, and invasion of U87 and U251 cells. Besides, we validated IGF1R as a direct target of miR-15b using dual luciferase assays, and IGF1R plasmids partially abrogated miR-15b mimics inhibited cell proliferation. In vivo, miR-15b mimics indeed repressed cell proliferation in mouse xenograft model. In conclusion, our study demonstrated that miR-15b inhibits the progression of glioblastoma cells through targeting IGF1R, and miR-15b can be recommended as a tumor suppressor in the progression of glioblastoma.

Keywords: Glioblastoma; IGF1R; miR-15b.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • Glioblastoma / genetics*
  • Glioblastoma / metabolism*
  • Glioblastoma / mortality
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / metabolism*
  • Receptor, IGF Type 1
  • Receptors, Somatomedin / metabolism*
  • Up-Regulation
  • Xenograft Model Antitumor Assays

Substances

  • IGF1R protein, human
  • MIRN15 microRNA, human
  • MicroRNAs
  • Receptors, Somatomedin
  • Receptor, IGF Type 1