Circular RNAs: Biomarkers of cancer

Abstract

Circular RNAs (circRNAs) are a class of single‐stranded closed RNAs that are produced by the back splicing of precursor mRNAs. The formation of circRNAs mainly involves intron‐pairing‐driven circularization, RNA‐binding protein (RBP)‐driven circularization, and lariat‐driven circularization. The vast majority of circRNAs are found in the cytoplasm, and some intron‐containing circRNAs are localized in the nucleus. CircRNAs have been found to function as microRNA (miRNA) sponges, interact with RBPs and translate proteins, and play an important regulatory role in the development and progression of cancer. CircRNAs exhibit tissue‐ and developmental stage–specific expression and are stable, with longer half‐lives than linear RNAs. CircRNAs have great potential as biomarkers for cancer diagnosis and prognosis, which is highlighted by their detectability in tissues, especially in fluid biopsy samples such as plasma, saliva, and urine. Here, we review the current studies on the properties and functions of circRNAs and their clinical application value.

Non-Coding RNAs in Human Cancer and Other Diseases: Overview of the Diagnostic Potential

“…They are ubiquitous across species but not highly conserved among different species ranging from viruses to mammals. Most circRNAs (84%) are created from protein-coding genes by an alternative splicing called backsplicing of pre-mRNAs, connecting the 3 splice end of the downstream exon to the 5 splice site of the upstream exon of genes containing long exons and flanking introns [35,36]. circRNA can be transported from the nucleus to the cytosol by specific mechanisms.…”

“…[33,38]. CircRNA can be involved in cancer pathogenesis in several ways: (a) acting through the miRNA sponge, circRNAs may serve as competitive inhibitors of miRNA and behave as oncogenes (e.g., circCDDC66 in colon cancer, circCCAC1 in cholangiocarcinoma, WHSC1 in endometrial and ovarian cancer, circANRIL in breast, bladder and gastric cancers, and circRNA_0000285 in cervical cancer [35]). circPCNXL2 and hsa_circ_001895 cause kidney cancer by inhibiting miR-153 and miR-296-5p, respectively.…”

“…circRNA hsa_circ_001783 in breast cancer acts through the miR-20c-3p sponge. circRNAs such as circHMGB2, cir-cIGF2BP3 and circUSP7 promote the development of non-small cell carcinoma [35,40]. (b) Acting through the miRNA sponge pathway or through other mechanisms, circR-NAs may behave as tumour suppressors (e.g., circHIPK3 in bladder cancer, circURI1 and hsa_circ_0014717, circORC5 in gastric cancer, circ-AKT3 in kidney cancer through the miR-296-3p sponge, and circPLCE1 in colon cancer) [33,39,40].…”

“…(b) Acting through the miRNA sponge pathway or through other mechanisms, circR-NAs may behave as tumour suppressors (e.g., circHIPK3 in bladder cancer, circURI1 and hsa_circ_0014717, circORC5 in gastric cancer, circ-AKT3 in kidney cancer through the miR-296-3p sponge, and circPLCE1 in colon cancer) [33,39,40]. circRNA isolated from various body fluids can serve as possible diagnostic or prognostic markers, determining different subtypes or different staging and grading of the tumours (e.g., circRMST from blood in medulloblastoma, hsa_circ_0014717, hsa_circ_0000190 or hsa_circRNA_102958 from blood or from stomach samples in gastric cancer, hsa_circ_0001874, and hsa_circ_0001971 from local samples in oral carcinoma, circPDLIM5, circSCAF8, circPLXDC2, circSCAMP1, and circCCNT2 collected from urine or blood in prostate cancer) [33,35,[38][39][40].…”

Vaccines’ New Era-RNA Vaccine

“…Current research on circRNA has unveiled several functional traits, including acting as a molecular sponge, regulating cell activity, and influencing protein translation. Moreover, circRNA’s association with specific human diseases endows it with the potential to serve as a novel disease biomarker and therapeutic target [ 17 , 18 ]. However, the precise physiological function of natural circRNA remains elusive.…”