Extracellular MicroRNAs as Intercellular Mediators and Noninvasive Biomarkers of Cancer

SIMPLE SUMMARY: There are an extensive number of publications regarding the role of endogenous miRNAs as regulators of gene expression in cancer. However, extracellular miRNAs have emerged as a novel mechanism of cell-to-cell communication in normal conditions and disease and have drawn a large amount of interest as regulators of gene expression and as potential non-invasive biomarkers in cancer. Despite this high interest and the abundance of research on the biology and role of extracellular miRNAs in cancer, they are not yet completely understood. The aim of this review is to highlight the relevant biological characteristics of extracellular miRNAs that enable them to function as intercellular mediators of gene expression regulation and provide the recently published evidence of the specific role of extracellular miRNAs in tumor development and progression. ABSTRACT: MicroRNAs (miRNAs) are released by different types of cells through highly regulated mechanisms under normal and pathological conditions. These extracellular miRNAs can be delivered into recipient cells for functional purposes, acting as cell-to-cell signaling mediators. It has been discovered that cancer cells release miRNAs into their surroundings, targeting normal cells or other cancer cells, presumably to promote tumor development and progression. These extracellular miRNAs are associated with oncogenic mechanisms and, because they can be quantified in blood and other bodily fluids, may be suitable noninvasive biomarkers for cancer detection. This review summarizes recent evidence of the role of extracellular miRNAs as intercellular mediators, with an emphasis on their role in the mechanisms of tumor development and progression and their potential value as biomarkers in solid tumors. It also highlights the biological characteristics of extracellular miRNAs that enable them to function as regulators of gene expression, such as biogenesis, gene silencing mechanisms, subcellular compartmentalization, and the functions and mechanisms of release.