Circular RNA: The evolving potential in the disease world

Table 2 Circular RNAs as potential biomarkers in major human cancers

Cancer	circRNA	Expression	Function/target	Ref.
Lung cancer	hsa_circ_0005962	Up	Promotes proliferation; non-invasive diagnostic biomarker	[80]
	hsa_circ_0086414	Down	Cancer progression; non-invasive diagnostic biomarker	[80]
	hsa_circ_0102537	Down	Biomarker for diagnosis; fluid shear stress and PI3K-Akt signaling pathway	[81]
	hsa_circ_0000190	Up	Tumorigenesis and immune evasion; facilitates tumorigenesis and immune evasion by upregulating the Expression of soluble PD-L1 in non-small-cell lung cancer	[82]
	CDR1as	Up	Enduring growth signaling; regulating miR-219a-5p/SOX5 axis	[83]
	hsa_circ_0001715	Up	Distant metastasis; potential diagnostic and prognostic Biomarker	[84]
	circPTK2	Down	Activating invasion and metastasis; inhibits TGF-β-induced epithelial-mesenchymal transition and metastasis by controlling TIF1γ	[85]
	circ_0067934	Up	Activating invasion and metastasis; regulating miR-1182/KLF8 axis and activating Wnt/β-catenin pathway	[86]
	hsa_circ_0012673	Up	Cancer cell proliferation and invasion; via miR-320a/LIMK18521 axis	[87]
	F-circEA-2a	Up	Promotes cell migration and invasion	[88]
	F-circEA	Up	Promotes cell migration and invasion; potential diagnostic value	[89]
	circRNA_100876	Up	Distant metastasis; potential prognostic biomarker and therapeutic target	[90]
	circRNA_ZEB1/hsa_circ_0023404	Up	Promotes proliferation, migration, and invasion; regulating miR-217/ZEB1 axis	[91]
	CiRS-7	Up	Increased proliferation, migration, and invasion, yet reduced apoptosis; targets NF-κB signaling	[92]
HCC	has_circ_0001445	Up	Regulates proliferation and migration; targets miR-942-5p/ALX4 axis	[93]
	has_circ_0027089	Up	Biomarker for diagnosis of hepatitis-related HCC	[94]
	has_circ_0016788	Up	Evading growth inhibitors; targets miR-486/CDK4 pathway	[95]
	circ-SMARCA5	Down	Inhibits cell proliferation and promotes apoptosis; potential prediction and monitoring biomarker for HCC	[96]
	circSMAD2	Down	Activating invasion and metastasis; inhibits epithelial-mesenchymal transition by targeting miR-629	[97]
	has_circ_0064428	Down	Immune-associated prognostic biomarker for HCC patients	[98]
	has_circ_0009582; circ_0037120	Up	Biomarker for diagnosis	[99]
	has_circ_0140117	Up	Potential biomarkers for predicting occurrence of HCC	[99]
	CDR1as	Up	Cell proliferation and migration; enduring growth signaling	[100]
Gastric cancer	has_circ_0010882	Up	Role in proliferation, migration, and invasive phenotypes; regulation of PI3K/Akt/mTOR signaling	[101]
	has_circ_0001017	Down	Cell proliferation, migration, and invasion; sponge of miR-197	[102]
	has_circ_0061276; hsa_circ_0001017	Down	Potential prognostic tumor biomarkers	[103]
	has_circ_0000745	Down	Regulating GC growth and migration; promising diagnostic biomarker	[104]
	circ-Rangap1	Up	Cancer invasion and metastasis; targeting miR-877-3p	[105]
	has_circ_0000181	Up	Distant metastasis and TNM stage; diagnostic biomarker	[106]
	circ-PSMC3	Down	Cell proliferation and metastasis	[107]
	circ-LMTK2	Down
	circ-DLST	Up
	circ-KIAA1244	Down	TNM stage and lymphatic metastasis	[108]
	circ-ZFR	Down	Evading growth inhibitors; sponging miR-130a/miR-107 and modulating PTEN	[109]
	CDR1as	Down	Evading growth inhibitors; targeting miR-876-5p/GNG7 axis	[110]
	circRNA-000425	Down	Evading growth inhibitors; proliferation, apoptosis, and cell drug sensitivity via YAP1-induced tumorigenesis	[111]
	circRNA_0023642	Up	Activating invasion and metastasis; regulating epithelial-mesenchymal transition	[112]
	has_circ_0001178	Up	Invasion and metastasis; via sponging multiple miRNAs	[113]
	has_circ_0005927	Down	Cell colony-forming ability, migration, and invasion; regulating miR-942-5p/BATF2 axis	[114]
	has_circ_0082182	Up	Drug resistance and cancer progression; sponging miR-326	[115]
	hsa_circ_0082182, hsa_circ_0000370	Up	Inhibit apoptosis; potential diagnostic markers	[116]
	has_circ_0035445	Up	Promotes proliferation and migration but suppresses apoptosis; potential diagnostic marker	[116]
	has_circ_0006990	Up	Cancer progression; via mediation of hsa_circ_0006990/miR-132-3p/MUC13 axis	[117]
	CDR1as	Up	Enduring growth signaling; regulating microRNA-7	[118]
	circHIPK3	Up	Enduring growth signaling; sponging miR-7	[119]
	hsa_circ_0007534	Up	Blocking apoptosis	[120]
	hsa_circRNA_103809	Down	Cell proliferation and migration; via miR-532-3p/FOXO4 axis	[121]
	hsa-circ-0020397	Up	Regulates CRC cell viability, apoptosis, and invasion by promoting the expression of miR-138 target genes	[121]
Breast cancer	hsa_circ_0001785	Up	Proliferation, migration, and invasion; potential diagnostic value	[122]
	hsa_circ_0008673	Up	Prognostic predictor of OS and DSS	[122]
	circ-ITCH	Down	Evading growth inhibitors; targets Wnt/β-catenin pathway	[123]
	hsa_circ_0104824	Down	Cell migration, cell-cell adhesion, and proliferation; promising predictive biomarker and therapeutic target	[124]
Esophageal cancer	circ-TTC17	Up	Promotes proliferation and migration; novel biomarker for diagnosis, treatment, and prognosis	[125]
	hsa_circ_0007203 (circ-DLG1)	Up	Promotes cell proliferation	[126]
	hsa_circ_0004771	Up	Diagnostic biomarker; targets via miR-339-5p/CDC25A axis	[127]
	circGSK3β	Up	Promoting metastasis; augmenting β-catenin signaling	[128]
	circ-SLC7A5	Up	Regulator of tumorigenesis and metastasis	[129]
Pancreatic cancer	circ-LDLRAD3	Up	Proliferation, migration and invasion; via miR-137-3p/PTN axis	[130,131]
	circNFIB1, hsa_circ_0086375	Down	Lymphangiogenesis and lymphatic metastasis; via miR-486-5p/PIK3R1/VEGF-C axis	[132]
Thyroid cancer	has_circ_0124055	Up	Regulates proliferation and apoptosis: Prognostic and diagnostic indicator	[133]
	has_circ_0101622	Up	Regulates proliferation and apoptosis: Prognostic and diagnostic indicator	[133]
Gallbladder cancer	circ-MTO1	Up	Early diagnostic and prognostic marker	[134]
	circHIPK3	Up	Evading growth inhibitors; sponging miR-124	[135]
Ovarian/endometrial cancer	has_circ_0078607	Up	Adverse prognostic indicator for ovarian cancer; regulating miR-32-5p/SIK1 network	[136]
	has_circ_0061140	Up	Activating invasion and metastasis; targeting miR-197/high mobility group protein A1 axis in endometrial cancer	[137]
Glioma/glioblastoma	hsa_circ_0046701	Up	Enduring growth signaling; critical regulatory roles via hsa_circ_0046701/miR-142-3p/ITGB8 axis	[138]
	circ-FBXW7	Down	Enduring growth signaling; potential prognostic implications	[139]
	circNFIX	Up	Blocking apoptosis; regulating miR-378e/RPN2 axis	[140]
	cZNF292	Up	Promoting angiogenesis; Wnt/β-catenin signaling	[141]

HCC: Hepatocellular carcinoma; OS: Overall survival; DSS: Disease-specific survival; TGF-β: Transforming growth factor-β; GC: Gastric cancer; circRNA: Circular RNAs.