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

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.