Article Figures & Data
Figures
- Figure 1.
Biogenesis and stability of circRNA. CircRNAs are formed from backsplicing the 5′ end of one exon to the 3′ end of another—in this figure, exon 5 onto 4 and exon 3 onto itself. Backspliced exons typically have longer flanking introns, as is the case between exon 3 and 4. The backspliced exons form covalently closed structures that may consist of one exon or multiple exons. Intronic DNA may be present as well. CircRNAs are resistant to degradation by exoribonucleases due to a lack of 3′ poly(A) tail. This enables them to be stable in plasma, urine, and saliva.
- Figure 2.
Proposed circRNA biologic functions. A, Function as competing endogenous RNA. CircRNA can bind miRNAs that negatively regulate mRNA to increase mRNA expression. Many circRNA/miRNA/mRNA axes have been reported with potential biologic significance. B, Function as protein scaffold. CircRNA can help form scaffolds to stabilize protein complexes, including those involving RBPs. C, Function as template for translation. Some circRNAs have internal ribosomal entry sites (IRES) and open-reading frames enabling translation. CircRNAs can also undergo multiple consecutive rounds of translation.
Tables
- Table 1.
Summary of publicly available circRNA databases.
Database Number of samples Total human circRNA Human/cancer specific? Detection tool Brief description Ref. Circ2Disease N/A 237 Yes/No N/A CircRNA associated with disease, reports interaction with miRNA (88) Circ2Traits 4 1,953 Yes/No find_circ Associate circRNA with disease and traits (89) circAtlas 2.0 240 421,501 No/No CIRI2, CIRCexplorer, DCC, MapSplice Diversity and similarity among circRNA and expression from multiple species (80) circBank 34 140,790 Yes/No Multiple sources Comprehensive database with predicted miRNA-binding sites (82) circBase 20 92,375 No/No Multiple sources Database of circRNA identified by RNA-seq on cell lines from multiple studies (79) CircFunBase N/A 3,799 No/No N/A Compendium of circRNA from various species with focus on reported functions (87) CircInteractome 34 140,790 Yes/No N/A Interaction between circRNA, miRNA, and potential transcripts (83) circNet 464 212,950 Yes/No find_circ CircRNA–miRNA–gene networks and reports circRNA expression (84) CIRCpedia v2 70 183,493 No/No CIRCexplorer2, MapSplice CircRNA across 6 different species (81) CircR2Disease N/A 661 Yes/No N/A CircRNA with known association with disease (90) circRNADb N/A 32,914 Yes/No Multiple sources Reports circRNA and possible transcripts as well as protein-coding potential (85) exoRBase 92 58,330 Yes/No ACFS, find_circ Characterize RNA (circRNA, lncRNA, mRNA) found in exosomes (94) TCSD 60 1,184,752 No/No CIRI, circRNA_finder, find_circ Tissue-specific circRNA in adult and fetal human and mouse tissue (32) Abbreviation: N/A, not applicable.
- Table 2.
Summary of publicly available cancer-specific circRNA databases.
Database Number of samples Total human circRNA Cancer specific? Detection tool Brief description Ref. BBCancer 7,184 175,508 Yes CIRI, find_circ Blood-based biomarkers, including circRNA in liver, colorectal, and pancreatic cancer (93) circPro 1 2,036 Yes CIRI2 Ribosome-associated circRNA with potential for translation into protein (86) CircRic 935 92,589 Yes CIRI2, CIRCexplorer2, circRNA_finder, find_circ CircRNA among cancer cell lines with integrative analysis and potential drug response (92) CSCD 228 1,394,023 Yes CIRI2, find_circ, circRNA_finder, CIRCexplorer Cancer-specific circRNA in cell lines and potential function (91) MiOncoCirc 2,000+ 160,120 Yes CIRCexplorer CircRNA in human cancer tissues by exome capture sequencing (53) - Table 3.
Sensitivity and specificity of reported differential circRNA expression in cancer plasma compared with normal patients for early cancer detection.
Primary cancer CircRNA Sensitivity Specificity AUC Ref. Lung circYWHAZ (hsa_circ_0005962) 77.8% 72.2% 0.81 (222) circBNC2 (hsa_circ_0086414) Lung circFARSA Not reported Not reported 0.71 (70) Lung circACP6 (hsa_circ_0013958) 75.5% 79.6% 0.815 (69) Breast circELP3 (hsa_circ_0001785) 76.4% 69.9% 0.784 (223) Colorectal circFAM71F2 (hsa_circ_0082182) Not reported Not reported 0.835 (224) circFLI1 (hsa_circ_0000370) circALDH1A2 (hsa_circ_0035445) Colorectal circCCDC66 64.4% 85.2% 0.780 (225) circABCC1 circSTIL Gastric circXPO1 (hsa_circ_0001017) 84.7% 96.6% 0.912 (75) circNRIP1 (hsa_circ_0061276) Gastric circLMO1 (hsa_circ_0021087) Not reported Not reported 0.773 (226) circUBXN7 (hsa_circ_0005051) Gastric circRPL6 Not reported Not reported 0.733 (227) Gastric circCNIH4 (hsa_circ_0000190) 41.4% 87.5% 0.60 (228) Gastric circSPECC1 (hsa_circ_0000745) 85.5% 45.0% 0.683 (229) Gastric circTATDN3 (hsa_circ_0000181) 99.0% 20.6% 0.582 (230) Pancreatic circLDLRAD3 57.4% 70.5% 0.67 (231) Liver circHPCAL1 (hsa_circ_0000976) 87.5% 84.0% 0.858 (Set 1) (232) circRABGGTA (hsa_circ_0007750) 85.5% 89.5% 0.875 (Set 2) circMTM1 (hsa_circ_0139897) Liver circSMARCA5 86.7% 89.3% 0.938 (233) Liver circSMARCA5 (hsa_circ_0001445) 71.2% 94.2% 0.862 (234) Oral (saliva) circBICD2 (hsa_circ_0001874) 92.7% 77.8% 0.922 (236) circFAM126A (hsa_circ_0001971)
Volume 29, Issue 12
