Role of METTL3 dependent m6A modification in glioma stem cell maintenance

The most aggressive form of astrocytoma is glioblastoma multiforme (GBM) and it has a worse prognosis with less than a 14-months average survival after diagnosis. Though cancer stem cells are of small population in tumor they posses high proliferative potential and cause resistance to routine therapy. Glioma Stem Cells which undergo dynamic transitions rely on reversible modifications of DNA and RNA for molecular functions. In addition, reversible nature of these modifications makes them valuable drug targets in cancer. The diverse functions of RNA are accompanied by more than 100 chemical modifications, although the functions of most of these RNA modifications remain elusive. METTL3 is an RNA methylase which adds m6A marks and it is upregulated in stem cell compartment compared to differentiated glioma cells. Though this gene is speculated to affect the RNA maturation process at different stages and results in altered mRNA levels in a cumulative manner, the exact role in glioma progression has not yet been reported. We studied the essential functions of this enzyme by identifying the global METTL3 mediated m6A landscape in GBM patient derived stem cells. The study of elucidating the molecular basis of METTL3 enzyme in GSC may impact the therapeutic aspects of GBM.