Abstract
The complexity of microRNA (miRNA)-mediated pathway control has burgeoned since the discovery that miRNAs are found in the extracellular space and constitute a form of cell-cell communication. miRNAs have been found in plasma, urine, and saliva and have recently been shown to be carried on lipoproteins. This has led to the proposal that circulating miRNAs may be useful biomarkers of various diseases, including cardiovascular disease, diabetes, and other forms of dysregulated metabolism. Although our understanding of the cellular machinery responsible for the secretion of miRNA is incomplete, it has been demonstrated that miRNAs are packaged into exosomes, microvesicles, and apoptotic bodies by a broad range of cell types. Intriguingly, a large portion of extracellular miRNA is found outside of any lipid-containing vesicle, and instead is associated with RNA binding proteins like argonautes 1 and 2, which may aid in their protection from abundant nucleases in the extracellular space. The excitement for miRNAs as biomarkers is mounting as more and more evidence supports that these noncoding RNAs are actively secreted from diseased tissues, possibly before the onset of overt disease. While caution should be taken in these early days, there is little doubt that extracellular miRNAs will hold tremendous potential as both diagnostic and therapeutic agents.