156 Poster - The role of enhancer RNAs in glioblastoma multiforme

Abstract

Background: Glioblastoma Multiforme (GBM) represents the most aggressive type of human brain cancer with dismal prognosis. Studies have revealed the presence of self-propagating cancer stem cells which exhibit increased phenotypic plasticity under the influence of the tumor microenvironment. Common therapies for GBM include surgical resection, radiation and adjuvant chemotherapy. Despite these therapeutic efforts, GBM has a 5-year survival of about 5%. Although DNA (genetic) variations account for 30– 50% of the abnormalities identified in GBM and other cancers, epigenetic abnormalities such as histone modifications and non-coding RNA species account for the remaining drivers of cancer. A decade ago, a new class of non-coding RNA termed enhancer RNA (eRNA) was discovered. It is accepted that the combinatorial binding of RNA Pol II and the histone mark H3K27Ac at specific enhancer regions mark active enhancers that can produce eRNAs. Multiple articles have demonstrated the presence and role of eRNAs in breast cancer, prostate cancer and macrophages; the main role being the regulation of gene transcription through stabilization of enhancer-promoter looping. However, the functional role of eRNAs in the maintenance of the glioma stem cell fate and the contribution of eRNAs to the reversible phenotypic transition of glioma stem cells are not known. We hypothesize that eRNAs are expressed in glioma stem cells and may modulate the activity of neighboring and stemness essential genes as well as regulate genome organization.