MiR-18a regulates the proliferation, migration and invasion of human glioblastoma cell by targeting neogenin

Exp Cell Res. 2014 May 15;324(1):54-64. doi: 10.1016/j.yexcr.2014.03.009. Epub 2014 Mar 21.

Abstract

MiR-17-92 cluster has recently been reported as an oncogene in some tumors. However, the association of miR-18a, an important member of this cluster, with glioblastoma remains unknown. Therefore, this study aims to investigate the expression of miR-18a in glioblastoma and its role in biological behavior of U87 and U251 human glioblastoma cell lines. Quantitative RT-PCR results showed that miR-18a was highly expressed in glioblastoma tissues and U87 and U251 cell lines compared with that in human brain tissues and primary normal human astrocytes, and the expression levels were increased along with the rising pathological grades of glioblastoma. Neogenin was identified as the target gene of miR-18a by dual-luciferase reporter assays. RT-PCR and western blot results showed that its expression levels were decreased along with the rising pathological grades of glioblastoma. Inhibition of miR-18a expression was established by transfecting exogenous miR-18a inhibitor into U87 and U251 cells, and its effects on the biological behavior of glioblastoma cells were studied using CCK-8 assay, transwell assay and flow cytometry. Inhibition of miR-18a expression in U87 and U251 cells significantly up-regulated neogenin, and dramatically suppressed the abilities of cell proliferation, migration and invasion, induced cell cycle arrest and promoted cellular apoptosis. Collectively, these results suggest that miR-18a may regulate biological behavior of human glioblastoma cells by targeting neogenin, and miR-18a can serve as a potential target in the treatment of glioblastoma.

Keywords: Glioblastoma; Invasion; MiR-18a; Migration; Neogenin; Proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Cell Cycle Checkpoints / genetics
  • Cell Movement / genetics*
  • Cell Proliferation*
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma / genetics*
  • Glioblastoma / pathology*
  • HEK293 Cells
  • Humans
  • Membrane Proteins / genetics*
  • MicroRNAs / physiology*
  • Neoplasm Invasiveness
  • Tumor Cells, Cultured

Substances

  • 3' Untranslated Regions
  • MIRN18A microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • neogenin