MicroRNA of extracellular vesicles as biomarkers and regulators of pathological and physiological processes

Abstract

Extracellular vesicles (EV) are currently considered potential biomarkers of diseases, as well as “biological constructs” for targeted drug delivery. Extracellular vesicles represent a heterogeneous population of membrane vesicles formed by various cell populations, including immune cells. At present time, EV are divided into exosomes, microvesicles, and apoptotic bodies, depending on their size and formation manner. EV have been found in various human biological fluids. Therefore, the possibility of their usage as diagnostic biomarkers is under discussion. The vesicles have a diverse internal composition and express a wide repertoire of receptors on their surface, thus allowing them to participate in different intercellular communications by transferring to the cells various molecules, including genetic material. E.g., microRNAs transmitted via extracellular vesicles are evolutionarily conserved non-coding RNA molecules 18-25 nucleotides long. Their main function is to regulate gene expression at the post-transcriptional level. MicroRNAs are synthesized by different cell types. However, some microRNAs are found ubiquitously, whereas others are present only in certain types of tissues. MicroRNAs are found both inside, and outside the cells (extracellular or circulating microRNAs). The microRNAs are resistant to RNases and stable in the extracellular environment, due to their secretion as protein complexes, or as part of extracellular vesicles. The variable microRNA profile in extracellular vesicles depends on the physiological conditions and presence of various pathological disorders. Multiple studies show that microRNAs can determine the functional activity of extracellular vesicles, e.g., therapeutic usage of microRNAs carried by EV as well as diagnostic applications in various pathologies. This review considers distinct populations of extracellular vesicles and their main properties, describes the characteristics of intra- and extracellular (circulating) microRNAs, mechanisms of their biosynthesis, and techniques for detection and assessing contents of microRNAs. The review describes microRNAs as a component of exosomes and microvesicles formed by various cells, including cells of the immune system in the course of physiological and pathological processes, with respect to functions of these microRNAs as well as their diagnostic and therapeutic potential.