The decade of exosomal long RNA species: an emerging cancer antagonist

Abstract

Exosomes have emerged as a novel approach for the treatment and diagnosis of cancer after RNA content was discovered in exosomes in 2007. As important meditators of intercellular communication, exosomes have become a strong focus of investigation for researchers in the past decade, as witnessed through the exponential increase of research on exosomes. The capability of exosomes to transfer functionally active cargo highlights their importance as promising biomarkers and diagnostic molecules, as well as prospective drug delivery systems. The accessibility of exosomes in nearly all biofluids additionally alludes to its unprecedented ability in various types of cancers due to its extensive impact on tumor formation and progression. This review analyzes the role of exosomal long RNA species, which is comprised of mRNA, lncRNA, and circRNA, in tumor formation and progression, with an emphasis on their potential as future diagnostic biomarkers and treatment vectors in cancer biology. Their alignment with the development of exosomal databases is further examined in this review, in view of the accumulation of studies published on exosomes in the past decade.

Keywords: Cancer biology; Exosome; Tumor formation and progression; circRNA; esRNA; lncRNA; mRNA.

Fig. 1

The biogenesis of exosomes. Beginning with endocytosis, the biogenesis of exosomes initially leads to the formation of endosomes. Further invagination of the endosomal membrane results in the incorporation of cytosolic protein or RNA within the endosome. The resulting multi-vesicular bodies (MVBs) then fuse with the plasma membrane and release the exosomes into the extracellular space, allowing the exosomes to interact with the recipient cells via endocytosis, direct fusion, or the binding of surface proteins. Once inside the recipient cells, RNA content, such as lncRNAs, can target proteins or epigenetic marks—affecting protein function and controlling the state of gene expression

Fig. 2

The role of exosomes in cancer biology. Due to their extensive effect on the tumor environment, released exosomes can promote angiogenesis and tumor metastasis, promote drug resistance, initiate immune responses, and advance cell proliferation and oncogenic cell transformation