Downregulation of microRNA-216b contributes to glioma cell growth and migration by promoting AEG-1-mediated signaling

Biomed Pharmacother. 2018 Aug:104:420-426. doi: 10.1016/j.biopha.2018.05.048. Epub 2018 May 25.

Abstract

Accumulating evidence indicates microRNA-216b (miR-216b) plays an important role in the development and progression of various cancers. However, little is known about the function of miR-216b in gliomas. In this study, we aimed to investigate the expression level and functional significance of miR-216b in gliomas. We found that miR-216b was significantly downregulated in glioma specimens and cell lines. Overexpression of miR-216b suppressed the growth and migration of glioma cells, while miR-216b inhibition showed the opposite effects. Astrocyte elevated gene-1 (AEG-1) was predicted as a potential target gene of miR-216b by bioinformatics analysis. A dual-luciferase reporter assay showed that miR-216b could directly target the 3'-untranslated region of AEG-1. RT-qPCR and western blot analysis showed that miR-216 negatively regulated AEG-1 expression in glioma cells. Correlation analysis revealed an inverse correlation between miR-216b and AEG-1 in clinical glioma specimens. miR-216b also regulated the activation of nuclear factor-κB and Wnt signaling in glioma cells. Moreover, restoration of AEG-1 expression partially reversed the inhibitory effect of miR-216b overexpression on glioma cell growth and migration. Overall, these results revealed a tumor suppressive role of miR-216b in glioma tumorigenesis, and identified AEG-1 as a target gene of miR-216b action. Our study suggests that miR-216b can be potentially targeted for the development of novel therapies for gliomas.

Keywords: AEG-1; Glioma; NF-κB; Wnt; miR-216b.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Astrocytes / pathology
  • Cell Adhesion Molecules / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Down-Regulation / genetics*
  • Gene Expression Regulation, Neoplastic / genetics
  • Glioma / genetics*
  • Glioma / pathology
  • Humans
  • Membrane Proteins
  • MicroRNAs / genetics*
  • RNA-Binding Proteins
  • Signal Transduction / genetics

Substances

  • 3' Untranslated Regions
  • Cell Adhesion Molecules
  • MIRN216 microRNA, human
  • MTDH protein, human
  • Membrane Proteins
  • MicroRNAs
  • RNA-Binding Proteins