RUNX3 is down-regulated in glioma by Myc-regulated miR-4295

J Cell Mol Med. 2016 Mar;20(3):518-25. doi: 10.1111/jcmm.12736. Epub 2016 Jan 12.

Abstract

MicroRNAs are increasingly reported as tumour suppressors that regulate gene expression after transcription. Our results demonstrated that miR-4295 is overexpression in glioma tissues and its level is significantly correlated with clinical stage. We also found that miR-4295 inhibited the cell G0/G1 arrest and apoptosis leading to promoted cell proliferation and activity. The murine modelling study revealed that female nude mice injected with U87/anti-miR-4295 exhibit subcutaneous tumours in the right groin. Compared with anti-NC, the tumour volume was significantly decreased in anti-miR-4295 treatment group. Furthermore, we confirmed miR-4295 mediates the expression of RUNX3 by targeting its 3'untranslation region. In addition, N-myc protein also could bind to the promoter of pri-miR-4295 and inhibit the expression of RUNX3 in glioma cells. These results validate a pathogenetic role of a miR-4295 in gliomas and establish a potentially regulatory and signalling pathway involving N-myc/miR-4295/RUNX3 in gliomas.

Keywords: N-myc; RUNX3; glioma; miR-4295.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Apoptosis
  • Base Sequence
  • Binding Sites
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism
  • Cell Line, Tumor
  • Core Binding Factor Alpha 3 Subunit / genetics
  • Core Binding Factor Alpha 3 Subunit / metabolism*
  • Female
  • G1 Phase Cell Cycle Checkpoints
  • Gene Expression Regulation, Neoplastic
  • Glioma / genetics
  • Glioma / metabolism*
  • Glioma / pathology
  • Humans
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Transplantation
  • Proto-Oncogene Proteins c-myc / physiology*
  • RNA Interference

Substances

  • 3' Untranslated Regions
  • Core Binding Factor Alpha 3 Subunit
  • MIRN4295 microRNA, human
  • MYC protein, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-myc
  • Runx3 protein, human