Extracellular Vesicles as Conduits of Non-Coding RNA Emission and Intercellular Transfer in Brain Tumors

Non-coding RNA (ncRNA) species have emerged in as molecular fingerprints and regulators of brain tumor pathogenesis and progression. While changes in ncRNA levels have been traditionally regarded as cell intrinsic there is mounting evidence for their extracellular and paracrine function. One of the key mechanisms that enables ncRNA to exit from cells is their selective packaging into extracellular vesicles (EVs), and trafficking in the extracellular space and biofluids. Vesicular export processes reduce intracellular levels of specific ncRNA in EV donor cells while creating a pool of EV-associated ncRNA in the extracellular space and biofluids that enables their uptake by other recipient cells; both aspects have functional consequences. Cancer cells produce several EV subtypes (exosomes, ectosomes), which differ in their ncRNA composition, properties and function. Several RNA biotypes have been identified in the cargo of brain tumor EVs, of which microRNAs are the most studied, but other species (snRNA, YRNA, tRNA, and lncRNA) are often more abundant. Of particular interest is the link between transforming oncogenes and the biogenesis, cargo, uptake and function of tumor-derived EV, including EV content of oncogenic RNA. The ncRNA repertoire of EVs isolated from cerebrospinal fluid and serum is being developed as a liquid biopsy platform in brain tumors.