The MYCN oncogene is frequently amplified in neuroblastoma and is associated with aggressive disease and treatment failure. MYCN induces expression of different miRNAs, which are posttranscriptional regulators of gene expression with established roles in neuroblastoma development.
In this study, we show that MYCN -amplified cell lines not only express miRNAs with functions inside the cell, but also secrete populations of miRNAs inside small vesicular structures called exosomes, with the ability to shuttle to other cells. We have isolated and characterised exosomes from MYCN amplified cell lines, and here demonstrate their ability to be taken up by other cells. By profiling the miRNA expression, we demonstrate high expression of a group of established on comirs in exosomes from two MYCN- amplified cell lines. Despite the fact that other studies have demonstrated the ability of exosomal miRNAs to regulate their targets in recipient cells, we did not observe this with exosomes from MYCN -amplified cells. However, exosomes were able to induce in vitro angiogenic tube formation, suggesting that they can have tumorigenic properties.
These new findings reveal a potential new way for MYCN -amplified neuroblastoma cells to interact with their environment.