Myc inhibition by Omomyc: genome wide analysis in glioblastoma cells

Omomyc is a Myc dominant interfering molecule with outstanding tumour suppressive efficacy. We employed an inducible Omomyc to investigate Myc inhibition in cells and cancer stem cells from glioblastoma, the most common and deadly brain tumour. Omomyc strongly affected proliferation, self-renewal and other key cancer cell properties. We investigated the mechanism involved through genome wide analysis of Omomyc binding to DNA, mRNA expression by RNA-seq and microRNA expression by RT-PCR arrays. We identified a set of mRNAs and microRNAs consistently modulated by Omomyc that are involved in controlling key aspects of glioblastoma cells. Finally, we identified novel histone modifications strongly correlated to Omomyc expression and present on Omomyc repressed genes. Omomyc tumour suppressive activity thus appears to result from epigenetic changes that affect the expression of mRNAs and microRNAs involved in gliomagenesis. Possible mechanisms will be discussed. Our data validate Myc inhibition as a powerful strategy for glioblastoma therapy.