Future directions of extracellular vesicle-associated miRNAs in metastasis.

Numerous studies have demonstrated the dynamic cell-to-cell communication mediated by extracellular vesicles (EV) in cancer cell survival and metastasis development. EV content includes proteins, lipids, DNA, and RNA like microRNAs. Non-protein coding microRNAs play a very active role in almost all cellular processes targeting mRNAs for silencing. Different miRNA profiles have been found in different cancer types, and clarification of miRNAs packed in EV from different types of cancers will allow the understanding of metastasis and the application of miRNAs as biomolecules in diagnostic, prognostic and therapeutic approaches to fight cancer. The profound review of Dhondt et al., 2016, provides a wide view of EV miRNAs involved in various steps of the metastasis process to illustrate how the cancer cell interaction with the near and long distance microenvironment allows metastasis. These studies will surely conduce to additional patient studies to prove the relevance of EV miRNAs in metastasis in vivo. It remains to be elucidated how the tumoral cell sorts the miRNAs for secretion to send a message, and to well recognize the type of EV performing this message delivering. It will be very useful to identify whether miRNAs are delivered with post-transcriptional modifications since this is an important feature for miRNAs activity and stability.