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.
Highlights
The complexity of microRNA-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
We understand that the secretion of miRNAs is a controlled, active, and specific process. miRNAs can be packaged into lipid-based carriers such as exosomes, microparticles, or apoptotic bodies, and have been found on lipoproteins like high- and low-density lipoprotein (HDL and LDL, respectively)
Vickers et al [27] were the first to demonstrate that human HDL and LDL have the capability to carry miRNAs in the core of the molecule hidden from the extracellular environment in serum, and most importantly these miRNAs can be transferred to recipient cells and alter target cell gene expression
Summary
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. The importance of miRNAs in the extracellular space has been exemplified by a number of studies showing specific and regulated export of miRNA from the cell, and the uptake and functional consequences in recipient cells.
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