MiR-508-5p Inhibits the Progression of Glioma by Targeting Glycoprotein Non-metastatic Melanoma B

Neurochem Res. 2016 Jul;41(7):1684-90. doi: 10.1007/s11064-016-1884-2. Epub 2016 Mar 22.

Abstract

Glioma is a severe and highly lethal brain cancer, a malignancy largely stemming from growing in a relatively restrained area of the brain. Hence, the understanding of the molecular regulation of the growth of glioma is critical for improving its treatment. MicroRNA has become a hotspot in research on diseases, especially in the initiation and progression of different types of cancer. However, the molecular function and mechanisms of miR-508-5p in gliomagenesis are still unclear. The aim of this study was to investigate miR-508-5p expression in glioma and determine its effects on proliferation. miR-508-5p expression levels, both in glioma cell lines and in tissue, were significantly lower than in a normal human astrocyte cell line or adjacent tissues. Cell growth was analyzed using a MTT assay and over-expression of miR-508-5p was found to decrease glioma cell growth. Moreover, a bioinformatic analysis was performed, showing that glycoprotein non-metastatic melanoma B (GPNMB) was a direct target for miR-508-5p in glioma cells. Furthermore, in vivo treatment with miR-508-5p reduced GPNMB protein levels in the tumor. Additionally, overexpression of GPNMB without 3'-UTR partially reversed the cell growth arrest induced by miR-508-5p over-expression in glioma cells. In conclusion, these results indicate that increased expression of miR-508-5p might be related to glioma progression, indicating a potential role of miR-508-5p for clinical therapy.

Keywords: Glioma; Glycoprotein non-metastatic melanoma B (GPNMB); Growth; MiR-508-5p; Xenograft.

MeSH terms

  • Animals
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / prevention & control
  • Cell Line, Tumor
  • Disease Progression*
  • Gene Targeting / methods
  • Glioma / metabolism*
  • Glioma / pathology
  • Glioma / prevention & control
  • Humans
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / biosynthesis*
  • Mice
  • Mice, Nude
  • MicroRNAs / administration & dosage
  • MicroRNAs / biosynthesis*
  • Tumor Burden
  • Xenograft Model Antitumor Assays / methods

Substances

  • GPNMB protein, human
  • MIRN508 microRNA, human
  • Membrane Glycoproteins
  • MicroRNAs