Glioma-derived miRNA-containing extracellular vesicles induce angiogenesis by reprogramming brain endothelial cells (miRNA-seq)

Glioblastoma multiforme (GBM) is characterized by the close relationship of glioma stem cells (GSC) with aberrant vascularization. It has been established that GSC-derived extracellular vesicles (GSC-EVs) and their cargoes are proangiogenic in vitro. To elucidate gene regulatory mechanisms of neovascularization both in vitro and in vivo, we performed RNA-seq and DNA methylation profiling of the response of human brain endothelial cells to GSC-EVs as well as histoepigenetic analysis of GBM molecular profiles in the TCGA collection. The gene regulatory responses showed a footprint of post-transcriptional gene silencing by EV-derived miRNAs. Remarkably, EVs and normal vascular growth factors stimulated highly distinct gene regulatory responses, both converging on angiogenesis, providing exciting new insight into targetable angiogenic signaling in GBM. In this study, DNA methylation and gene expression profiling by long-RNA-seq and small-RNA-seq were performed on cultured human brain microvascular endothelial cells to investigate expression patterns of angiogenesis.