Dual Functional MicroRNA-186-5p Targets both FGF2 and RelA to Suppress Tumorigenesis of Glioblastoma Multiforme

Cell Mol Neurobiol. 2017 Nov;37(8):1433-1442. doi: 10.1007/s10571-017-0474-4. Epub 2017 Feb 17.

Abstract

Glioblastoma multiforme (GBM) is one of the most malignant cancers. MicroRNAs (miRs) were reported to play important roles in GBM recently. However, the role of a novel miR-186-5p in GBM tumorigenesis is still elusive. Using bioinformatics, miR-186-5p was identified as potential regulators of both fibroblast growth factor (FGF)-2 and NF-κB subunit RelA. Luciferase reporter assay was used to confirm the direct recognition FGF2 and RelA mRNAs by miR-186-5p. Invasion and migration assays were employed to study the effect of miR-186-5p on GBM cell growth in vitro. Xenograft tumor animal model was established to elucidate the in vivo function of miR-186-5p. MiR-186-5p directly targeted mRNAs of both FGF2 and RelA, and repressed their expressions. Invasive and migratory abilities of GBM cells and growth of xenograft tumors were significantly inhibited by miR-186-5p, which can be restored by re-introduction of FGF2 and RelA expressions. MiR-186-5p is a novel tumor suppressor miR that functions to inhibit tumorigenesis of GBM both in vitro and in vivo, by targeting both FGF2 and RelA. MiR-186-5p/FGF2/RelA pathway may be potentially used as molecular targets of in the clinical treatment of GBM.

Keywords: Fibroblast growth factor (FGF)-2; Glioblastoma multiforme (GBM); MicroRNAs (miRs); Tumorigenesis.

MeSH terms

  • Animals
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism*
  • Carcinogenesis / pathology
  • Cell Line, Tumor
  • Fibroblast Growth Factor 2 / antagonists & inhibitors
  • Fibroblast Growth Factor 2 / biosynthesis*
  • Fibroblast Growth Factor 2 / genetics
  • Genes, Tumor Suppressor / physiology
  • Glioblastoma / genetics
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Transcription Factor RelA / antagonists & inhibitors
  • Transcription Factor RelA / biosynthesis*
  • Transcription Factor RelA / genetics
  • Xenograft Model Antitumor Assays / methods

Substances

  • MIRN186 microRNA, human
  • MicroRNAs
  • RELA protein, human
  • Transcription Factor RelA
  • Fibroblast Growth Factor 2