Exosomal circRNAs: biogenesis, effect and application in human diseases

Abstract

Exosomes have emerged as critical mediators of intercellular communication, both locally and systemically, by regulating a diverse range of biological processes between cells. Circular RNA (circRNA) is a novel member of endogenous noncoding RNAs with widespread distribution and diverse cellular functions. Recently, circular RNAs have been identified for their enrichment and stability in exosomes. In this review, we outline the origin, biogenesis and function of exosomal circRNAs as well as their roles in various diseases. Although their precise roles and mechanisms of gene regulation remain largely elusive, exosomal circRNAs have potential applications as disease biomarkers and novel therapeutic targets.

Keywords: Biomarker; CircRNA; Exosomal circRNA; Exosome; Tumor microenvironment.

Fig. 1

Origin and biogenesis of exosomal circRNAs in various diseases. Most cells secrete exosomes under different physiological and pathophysiological conditions. CircRNAs can be transferred through exosomes between donor cells and recipient cells as a messenger to mediate multiple signaling pathways

Fig. 2

Schematic illustration of the role of exosomal circRNAs in cell proliferation. Chronic exposure to arsenite increases exosomal circRNA_100284 levels, which accelerate the cell cycle and promote proliferation by acting on miR217. E2H2 and cyclin D1, promising biomarkers of proliferation, are extensively activated to regulate the G1 to S phase transition, thus inducing cell proliferation

Fig. 3

The role of exosomal circRNAs in metastasis. Exosomal circPDE8A acted as a competing endogenous RNA sponge with miR-338 and induced invasive growth via the MACC1, MET, ERK, and AKT pathways. Eventually, this process led to an increase in vascular endothelial permeability and promoted pancreatic tumor hepatic metastasis