Red Blood Cells as Potential Repositories of MicroRNAs in the Circulatory System

The amount of erythrocyte-derived microRNAs (miRNAs) represents the majority of miRNAs expressed in whole blood. miR-451, miR-144, and miR-486, which are abundant in red blood cells (RBCs), are involved in the process of erythropoiesis and disease occurrence. Moreover, erythrocyte-derived miRNAs have been reported to be potential biomarkers of specific diseases. However, the function and underlying mechanisms of miRNAs derived from erythrocytes remain unclear. Based on a review of previously published literature, we discuss several possible pathways by which RBC miRNAs may function and propose that RBCs may serve as repositories of miRNAs in the circulatory system and participate in the regulation of gene expression mainly via the transfer of miRNAs from erythrocyte extracellular vesicles (EVs). In the whole blood, there are still other important cell types such as leukocytes and platelets harboring functional miRNAs, and hemolysis also exists, which limit the abundance of miRNAs as disease biomarkers, and thus, miRNA studies on RBCs may be impacted. In the future, the role of RBCs in the regulation of normal physiological functions of the body and the entire circulatory system under pathological states, if any, remains to be determined.