M6A RNA MODIfiCATION AND A DRIVER OF CELLULAR PLASTICITY AND INTRA-TUMOURAL HETEROGENEITY IN GLIOBLASTOMA

Abstract AIMS The immense cellular plasticity of glioblastoma is a barrier to successful therapy. N6-methyladenosine (m6A) methylation RNA increasingly recognised as key driver differentiation. Crucially, it reversible and dynamic modification that alters phenotype via the regulation mRNA metabolism. We hypothesise m6A mediates plasticity, regulating transcriptional networks thus influencing adaptation under different microenvironmental conditions. Our aims are assess whether total levels m6A-regulatory gene expression responsive change in oxygenation confluency. Furthermore, we aim characterise spatial distribution 3D cell culture models. METHOD have investigated patient-derived lines from invasive region adult glioblastoma. Mass spectrometry anti-m6A immunofluorescence confocal microscopy was used quantify levels. compared normoxic versus hypoxic conditions low high confluency 2D culture, including migration during scratch assay. measured genes using rtPCR. RESULTS Total regulatory were not significantly However, decreased will further models microscopy. CONCLUSIONS demonstrate degree variability response micro-environmental conditions, such These findings indicate role for tumoral heterogeneity adaptation.