Extracellular/Circulating MicroRNAs: Release Mechanisms, Functions and Challenges

MicroRNAs (miRNAs) are endogenously initiated, small non-coding RNAs and typically regulate the expression of mRNAs in post transcriptional level either via translational repression or mRNA degradation. Aberrant expression of miRNAs is observed in diverse disease and altered physiological states. Recently, it has been revealed that miRNAs are not only present in cells but also in extracellular milieu especially in different bio-fluids including blood plasma, follicular fluid and even in cell culture media. Such extracellular miRNAs (ECmiRNAs) are remarkably stable in the extracellular harsh environment with the presence of high RNAse activity. Although the precise mechanisms of release of cellular miRNAs to extracellular environment remain largely unknown, recent studies suggest that the expression of these ECmiRNAs can be associated with patho-physiological condition of an organism. Moreover, these ECmiRNAs may deliver to the recipient cells via certain pathways where they can regulate translational activity of target genes. This review will discuss the nature and stability of ECmiRNAs along with their release mechanisms. Furthermore, based on recent evidences, it also summarizes the possible function of these ECmiRNAs in distant cell-to-cell communication and the difficulties we may face during ECmiRNA research.