Cell-free microRNAs as cancer biomarkers: the odyssey of miRNAs through body fluids

Cell-free microRNAs (cfmiRNAs), also known as extracellular or secretory microRNAs, are an emerging class of miRNAs that are released or secreted by cells. These miRNAs are transferred through various body fluids. A growing body of research has recently revealed that cancer cells also secrete their distinctive cfmiRNAs to the extracellular environment highlighting the contribution of cfmiRNAs to cancer progression. CfmiRNAs show high stability in the body fluids. Three pathways have been proposed for their entry into the body fluids: passive release from broken, injured and dead cells; active secretion through microvesicles; and active secretion via microvesicle-free protein-dependent route. Active pathways seem to play leading roles in the delivery of miRNAs. Detection of cfmiRNAs is of particular relevance to their translation into the clinic. Much effort has been devoted to the development of highly sensitive and efficient approaches for detection purposes. Nevertheless, some barriers such as finding a unique internal control for all cancer types remain to be bypassed. This review aims to provide an insight into the promises represented by cfmiRNAs as cancer biomarkers and describes advances made in the identification of numerous types of extracellular miRNAs that have potential for use in the diagnosis of a variety of cancers.