Circular RNA and its potential as prostate cancer biomarkers

Figure 1 Biogenesis of circRNAs. A: In backsplicing, circRNAs are usually flanked by the canonical splicing motifs, AG-GT, and covalently fuse the 5′ site of an upstream exon (acceptor) with the 3′ end of a downstream exon (donor); B: In the exon skipping model, an unstable intermediate lariat consisting of introns and skipped exons are generated after splicing. The intermediate lariat is then spliced to produce circRNA; C: Flanking introns containing complementary sequences (Alu repeats) bind and increase the possibility of backsplicing; D: RNA-binding proteins, such as Quaking can bind to flanking introns and dimerize to create a closed RNA loop which facilitates backsplicing. QKI: Quaking.

Figure 2 The disproportion of circRNAs between tumor and plasma. A: CircRNAs can be selectively enriched in exosomes and actively released into plasma as exosomes. During PCa progression, the integrity of normal prostatic tissues will be interrupted; this facilitates the release of circRNAs into the bloodstream; B: Stresses such as hypoxia, inflammation, and anti-tumor therapies will cause cell death and increase the release of circRNAs. Microparticles containing circRNAs shed from the metastasizing tumor will subsequently increase the circRNA concentration in plasma.