Abstract
Circular RNA (circRNA) is a type of non-coding RNA that forms a covalently closed continuous loop. The expression pattern of circRNA varies among cell types and tissues, and many circRNAs are aberrantly expressed in various cancers. Aberrantly expressed circRNAs have been shown to play crucial roles in carcinogenesis, functioning as microRNA sponges or new templates for protein translation. Recent research has shown that circRNAs are enriched in exosomes. Exosomes are secretory vesicles that mediate intercellular communication through the delivery of cargo, including proteins, lipids, DNA, and RNA. Exosome-mediated crosstalk between cancer cells and the tumor microenvironment promotes the epithelial-mesenchymal transition, angiogenesis, and immune escape, and thus may contribute to cancer invasion and metastasis. In this review, we discuss the biological functions of exosomal circRNAs and their significance in cancer progression. Additionally, we discuss the potential clinical applications of exosomal circRNAs as biomarkers and in cancer therapy.
Highlights
Exosomes are secreted vesicles 30–100 nm in diameter that contain host cell-derived cargo, including proteins, lipids, DNA, and RNA
RNA interference screening using short hairpin RNAs that target back-splicing junctions and linear transcripts outside of Circular RNA (circRNA) exons, to assess distinct functions of circRNAs and their parental linear RNAs in prostate cancer cells, revealed that 171 circRNAs were essential for proliferation, whereas their linear counterparts were not (Chen S. et al, 2019). These results show that circRNAs are not mere byproducts of splicing, but play important roles in carcinogenesis independent of their linear transcripts
The expression levels of circRNAs were barely altered after incubation at room temperature for up to 24 h (Li et al, 2015). These results indicate that circRNAs are highly enriched and stable in exosomes
Summary
Exosomes are secreted vesicles 30–100 nm in diameter that contain host cell-derived cargo, including proteins, lipids, DNA, and RNA. Exosomal circRNA_100284 accelerates the cell cycle and promotes cell proliferation by acting as a sponge of miR-271 and thereby upregulating EZH2 (Dai et al, 2018). In HCC cells, upregulated CDR1-AS accelerates cell proliferation and migration by acting as a sponge for miR-1270, promoting the expression of alpha-fetoprotein.
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