Opinion Review
Copyright ©The Author(s) 2024.
World J Med Genet. Sep 20, 2024; 12(1): 93011
Published online Sep 20, 2024. doi: 10.5496/wjmg.v12.i1.93011
Table 1 Circular RNAs as potential biomarkers in major human diseases
Body system
Disease
circRNA
Expression
Ref.
CardiovascularMyocardial infarctioncircRNA_081881Down[43]
MICRAUp
Cardiac fibrosiscircRNA_010567Up[44]
Congenital heart diseasehsa_circ_004183Down[45]
hsa_circ_079265
hsa_circ_105039
Hypertensionhsa_circ_0037911Up[46]
CardiomyopathycircDNAJC6Down[47]
circTMEM56
circMBOAT2
Heart failurehsa_circ_0062960Up[48]
Coronary artery diseasehsa_circ_0124644Down[49]
hsa_circ_0001879Down[50]
hsa_circ_0004104Down[51]
hsa_circ_0001445Up
Atrial fibrillationhsa_circ_025016Up[52]
Central nervous systemMoyamoya diseasehsa_circRNA_089761Down[53]
hsa_circRNA_100914
hsa_circRNA_089763
Temporal lobe epilepsycirc-EFCAB2 Up[54]
circ-DROSHADown[55]
circRNA-0067835Down
Alzheimer’s diseaseCDR1as/ciRS-7Down[56,57]
circPVT1Up[58]
Parkinson’s diseaseCDR1as/ciRS-7Up[59]
circzip-2
Multiple sclerosiscirc_0005402Down[60]
circ_0035560[61]
Prion diseaseCDR1as/ciR-7Up[56,62]
Psychiatry Schizophreniahsa_circRNA_104597Down[63]
RespiratoryTuberculosishsa_circRNA_001937Up[64]
hsa_circRNA_005086Up[35]
hsa_circRNA_009024Up
hsa_circRNA_104964Down
hsa_circRNA_102101Down
hsa_circRNA_104296Down
Siliocosishsa_circ_0058493Up[65]
circRNA-012091Down[66]
Pulmonary hypertensioncirc-GSAPDown[67]
circ_0068481Up[68]
Acute respiratory distress syndromehsa_circRNA_101952Up[69]
hsa_circRNA_101523Up
hsa_circRNA_102927Down
hsa_circRNA_100562Down
hsa_circRNA_102034Down
EndocrineDiabetes mellitusCiRS-7Up[70]
hsa_circ_0068087[71]
hsa_circ_0124636[71]
hsa_circ_0139110
hsa_circ_0054633
Diabetes/glucoseCDR1as/cirRS-7Up[70,72]
Homeostasis/CVDcircRNA-HIPK3Up[73]
circRNA-WDR77Up
circANKRD36Up
Diabetic cardiomyopathycircRNA_000203Up[74]
circRNA_010567Up[44]
hsa-circ-0076631Up[75]
Diabetic nephropathycircRNA_15698Up[59,75,76]
Gestational diabetescirc_5824Down[75]
circ_3636Down
circ_0395Down
Diabetic retinopathycircRNA-0005015Up[75]
circRNA-HIPK3Up[77]
cZNF609Up[78]
circRNA-cPWWP2AUp[79]
Table 2 Circular RNAs as potential biomarkers in major human cancers
Cancer
circRNA
Expression
Function/target
Ref.
Lung cancerhsa_circ_0005962UpPromotes proliferation; non-invasive diagnostic biomarker[80]
hsa_circ_0086414DownCancer progression; non-invasive diagnostic biomarker[80]
hsa_circ_0102537DownBiomarker for diagnosis; fluid shear stress and PI3K-Akt signaling pathway[81]
hsa_circ_0000190UpTumorigenesis and immune evasion; facilitates tumorigenesis and immune evasion by upregulating the Expression of soluble PD-L1 in non-small-cell lung cancer[82]
CDR1as
UpEnduring growth signaling; regulating miR-219a-5p/SOX5 axis[83]
hsa_circ_0001715UpDistant metastasis; potential diagnostic and prognostic Biomarker[84]
circPTK2DownActivating invasion and metastasis; inhibits TGF-β-induced epithelial-mesenchymal transition and metastasis by controlling TIF1γ[85]
circ_0067934UpActivating invasion and metastasis; regulating miR-1182/KLF8 axis and activating Wnt/β-catenin pathway[86]
hsa_circ_0012673UpCancer cell proliferation and invasion; via miR-320a/LIMK18521 axis[87]
F-circEA-2aUpPromotes cell migration and invasion[88]
F-circEAUpPromotes cell migration and invasion; potential diagnostic value[89]
circRNA_100876UpDistant metastasis; potential prognostic biomarker and therapeutic target[90]
circRNA_ZEB1/hsa_circ_0023404UpPromotes proliferation, migration, and invasion; regulating miR-217/ZEB1 axis[91]
CiRS-7UpIncreased proliferation, migration, and invasion, yet reduced apoptosis; targets NF-κB signaling[92]
HCChas_circ_0001445UpRegulates proliferation and migration; targets miR-942-5p/ALX4 axis[93]
has_circ_0027089UpBiomarker for diagnosis of hepatitis-related HCC
[94]
has_circ_0016788UpEvading growth inhibitors; targets miR-486/CDK4 pathway[95]
circ-SMARCA5DownInhibits cell proliferation and promotes apoptosis; potential prediction and monitoring biomarker for HCC[96]
circSMAD2DownActivating invasion and metastasis; inhibits epithelial-mesenchymal transition by targeting miR-629[97]
has_circ_0064428DownImmune-associated prognostic biomarker for HCC patients[98]
has_circ_0009582; circ_0037120UpBiomarker for diagnosis[99]
has_circ_0140117UpPotential biomarkers for predicting occurrence of HCC[99]
CDR1as
UpCell proliferation and migration; enduring growth signaling[100]
Gastric cancerhas_circ_0010882UpRole in proliferation, migration, and invasive phenotypes; regulation of PI3K/Akt/mTOR signaling[101]
has_circ_0001017DownCell proliferation, migration, and invasion; sponge of miR-197[102]
has_circ_0061276; hsa_circ_0001017DownPotential prognostic tumor biomarkers[103]
has_circ_0000745DownRegulating GC growth and migration; promising diagnostic biomarker[104]
circ-Rangap1UpCancer invasion and metastasis; targeting miR-877-3p[105]
has_circ_0000181UpDistant metastasis and TNM stage; diagnostic biomarker[106]
circ-PSMC3DownCell proliferation and metastasis[107]
circ-LMTK2Down
circ-DLSTUp
circ-KIAA1244DownTNM stage and lymphatic metastasis[108]
circ-ZFRDownEvading growth inhibitors; sponging miR-130a/miR-107 and modulating PTEN[109]
CDR1asDownEvading growth inhibitors; targeting miR-876-5p/GNG7 axis[110]
circRNA-000425DownEvading growth inhibitors; proliferation, apoptosis, and cell drug sensitivity via YAP1-induced tumorigenesis[111]
circRNA_0023642UpActivating invasion and metastasis; regulating epithelial-mesenchymal transition[112]
has_circ_0001178UpInvasion and metastasis; via sponging multiple miRNAs[113]
has_circ_0005927DownCell colony-forming ability, migration, and invasion; regulating miR-942-5p/BATF2 axis[114]
has_circ_0082182UpDrug resistance and cancer progression; sponging miR-326[115]
hsa_circ_0082182, hsa_circ_0000370UpInhibit apoptosis; potential diagnostic markers[116]
has_circ_0035445UpPromotes proliferation and migration but suppresses apoptosis; potential diagnostic marker[116]
has_circ_0006990UpCancer progression; via mediation of hsa_circ_0006990/miR-132-3p/MUC13 axis[117]
CDR1as
UpEnduring growth signaling; regulating microRNA-7[118]
circHIPK3UpEnduring growth signaling; sponging miR-7[119]
hsa_circ_0007534UpBlocking apoptosis[120]
hsa_circRNA_103809DownCell proliferation and migration; via miR-532-3p/FOXO4 axis[121]
hsa-circ-0020397UpRegulates CRC cell viability, apoptosis, and invasion by promoting the expression of miR-138 target genes[121]
Breast cancerhsa_circ_0001785UpProliferation, migration, and invasion; potential diagnostic value[122]
hsa_circ_0008673UpPrognostic predictor of OS and DSS[122]
circ-ITCHDownEvading growth inhibitors; targets Wnt/β-catenin pathway[123]
hsa_circ_0104824DownCell migration, cell-cell adhesion, and proliferation; promising predictive biomarker and therapeutic target[124]
Esophageal cancercirc-TTC17UpPromotes proliferation and migration; novel biomarker for diagnosis, treatment, and prognosis[125]
hsa_circ_0007203 (circ-DLG1)UpPromotes cell proliferation[126]
hsa_circ_0004771UpDiagnostic biomarker; targets via miR-339-5p/CDC25A axis[127]
circGSK3βUpPromoting metastasis; augmenting β-catenin signaling[128]
circ-SLC7A5UpRegulator of tumorigenesis and metastasis[129]
Pancreatic cancercirc-LDLRAD3UpProliferation, migration and invasion; via miR-137-3p/PTN axis[130,131]
circNFIB1, hsa_circ_0086375DownLymphangiogenesis and lymphatic metastasis; via miR-486-5p/PIK3R1/VEGF-C axis[132]
Thyroid cancerhas_circ_0124055UpRegulates proliferation and apoptosis: Prognostic and diagnostic indicator[133]
has_circ_0101622UpRegulates proliferation and apoptosis: Prognostic and diagnostic indicator[133]
Gallbladder cancercirc-MTO1UpEarly diagnostic and prognostic marker[134]
circHIPK3UpEvading growth inhibitors; sponging miR-124[135]
Ovarian/endometrial cancerhas_circ_0078607UpAdverse prognostic indicator for ovarian cancer; regulating miR-32-5p/SIK1 network[136]
has_circ_0061140UpActivating invasion and metastasis; targeting miR-197/high mobility group protein A1 axis in endometrial cancer
[137]
Glioma/glioblastoma
hsa_circ_0046701UpEnduring growth signaling; critical regulatory roles via hsa_circ_0046701/miR-142-3p/ITGB8 axis[138]
circ-FBXW7DownEnduring growth signaling; potential prognostic implications[139]
circNFIXUpBlocking apoptosis; regulating miR-378e/RPN2 axis[140]
cZNF292UpPromoting angiogenesis; Wnt/β-catenin signaling[141]
Table 3 Genome-wide identification of circular RNAs: How it began
Ref.
Genome-wide identification of circRNAs
Salzman et al[18], 2012Aimed to distinguish cancer-specific exon scrambling events
Identified 2748 scrambled isoforms in Hela and H9 embryonic stem cells
Conclusion: 98% of scrambled isoforms represent circRNAs
Jeck et al[8], 2013Classified circular transcripts based on their levels of abundance using three stringencies categories (low, medium, high)
Conclusion: circRNAs are conserved, stable, and nonrandom products of RNA splicing that could be involved in the control of gene expression
Memczak et al[7], 2013Developed a computational method to detect circRNAs
Conclusion: circRNAs form a significant class of post-transcriptional regulators
Guo et al[19], 2014Identified and quantified human circRNAs from ENCODE Ribozero RNA-seq data
Conclusion: Most circRNAs are nonsignificant side-products of splicing error
Zhang et al[20], 2014Developed CIRCexplorer to distinguish thousands of circRNAs in humans with p(A)-wloRNase R RNA-seq data
Conclusion: Alternative circularization paired with alternative splicing can generate additional circRNAs from one gene, which is suggestive of the new line of complexity in gene regulation