Long-distance intercellular miRNA transfer. In addition to short-distance miRNA exchange, for example, via gap junctions or during immunological synapse formation,21 ,22 miRNAs can also be released by cells either into extracellular vesicles or complexed to proteins for long-distance communication. These packaged, mature miRNAs and pre-miRNAs are protected from extracellular ribonuclease activity and can be taken up by recipient cells, where they influence cellular processes. (A) During “plasma membrane budding,” ectosomes containing cytoplasmic components like miRNAs are released into the extracellular surrounding. (B) The fusion of exocytic multivesicular bodies (MVBs) with the plasma membrane releases miRNA-containing intraluminal vesicles called exosomes. When derived from healthy cells, exosomes reach a diameter of 60 to 90 nm. Exosomes released by cancer cells were reported to differ in size or to display metastasis-associated surface markers.29 ,30 (C) The ABCA1 transporter mediates the release of HDL-complexed miRNAs.19 (D) Apoptotic bodies are released from a cell that undergoes apoptosis. These large vesicles contain fragmented DNA and cytoplasmic components including miRNAs. General mechanisms of vesicle uptake in recipient cells involve (E) endocytosis, (F) phagocytosis, and (G) fusion with the plasma membrane. The uptake of HDL-complexed miRNAs in recipient cells is mediated by (H) SR-B1 receptors.19 Release and uptake mechanisms of extravesicular AGO- or NPM-1–complexed miRNAs are not described yet.
