Table 1.

Oncogenic exo-circRNAs and their role in lung cancer

Exo-circRNA	Number of clinical samples	Types of samples	Animal model	Expression	Target genes	Mechanisms	Functions	Refs
CDR1-AS	104 LUAD patients	PAEC, LUAD PC9, A549	–	Up	PTX, CDDP	EGFR/PI3K pathway	Independent prognostic biomarker for LUAD patients	[165]
hsa_circ_0014235	Tumor tissues 35 samples and adjacent 35 samples	A549, H1299, 16HBE	Nude mice	Up	miR-520a-5p, DDP, CDK4	miR-520a-5p/CDK4 regulatory axis	An increase in DDP resistance and promotion of cancerous cell activity	[100]
hsa_circ_0056616	42 lung adenocarcinomas with lymph node metastases, 48 without	PC9, PC14	–	Up	CXCR4	–	CXCR4 knockdown inhibits colony formation, cell proliferation, migration, and invasiveness	[82]
Circ-MAN2B2	–	BESA-2B, A549, H226, H1299, H446	–	Up	miR-1275, FOXK1	CircMAN2B2/miR-1275/FOXK1 signaling	Act as an oncogene, which promotes lung cancer cell proliferation and invasion	[166]
hsa_circ_0013958	49 pairs of LAC samples	A549, H1299, BEAS-2B	–	Up	miR-34, CCND1	–	Encouraging cell growth and invasion while discouraging cell death	[167]
hsa-circRNA-002178	105 paired LUAD and noncancerous tissue samples	95D, PC9, A549, BEAS-2B	–	Up	miR-34a, miR-28-5p, PDL1, PD1	–	Increase PDL1 and PD1 expression in tumor cells	[168]
Circ-CPA4	NSCLC patients (N = 50)	cA549, H1299, SK-MES-1, Calu-3, HBE	Nude mice	Up	miR-134, let-7 miRNA, PD-L1	Let-7 miRNA/PDL-1 axis	Immunity evasion	[169]
CircFARSA	10 pairs of tumor and adjacent normal tissues	A549	–	Up	miR-330-5p, miR-1270, miR-1178-3p, miR-620, miR-326	–	A novel biomarker for NSCLC	[170]
Circ_0014130(circPIP5K1A)	–	H1299, PC9, H1975, A549, H1650, BEAS‐2B	Nude mice	Up	miR-600, HIF‐1α gene 3′‐UTR	CircPIP5K1A/miR‐600/HIF‐1α axis	MiR600 reduced HIF1-mediated metastasis and cancer growth	[171]
Circ_RAD23B	40 NSCLC samples and paired adjacent normal tissue specimens	H1299, H1581, H358, A549, 16HBE	–	Up	miR593-3p, miR-653-5p, CCND2, TIAM1	MiR-593e3p/CCND2 axis, and miR-653e5p/TIAM1 pathway	Function as oncogene by miRNA sponge	[172]
CircPVT1	–	–	–	Up	miR-124-3p, EZH2	MiR-124-3p/EZH2 axis	Exosomal circPVT1 enhances proliferation and metastasis by polarizing macrophages through miR-124-3p/EZH2	[85]
Circ-MEMO1	Tissue samples 52 tumor and adjacent normal	H1650, A549, H1299, PC9, HBE	Nude mice	Up	miR-101-3p, 3′’ UTR of KRAS	MiR-101-3p/KRAS Axis	MiR-101-3p targeting KRAS increased NSCLC progression and glycolysis	[173]
	Serum samples; 30 patients and 25 healthy
Circ-PRMT5	90 pairs of cancer and adjacent normal tissues	A549, 95-D, HCC827, H1299, SK-MES-1, HBE	Nude mice	Up	miR-377/382/498	MiR-377/382/498-EZH2	Circ-PRMT5 promotes NSCLC growth by miR-377/382/498 sponging and upregulating EZH2	[174]
						pathway
CircHIPK3	3 different primary lung cancer	A549, BEAS-2B	–	Up	miR124	CircHIPK3-miR-124 pathway	Promotes lung cancer cell progression via miRNA sponging	[175]
	patients
CircRNA CCDC66	628 patients with newly diagnosed NSCLC	H125, H23, H226, H838, H1437, H2009, H2087, A549, H125, H23, H838, H1437, H2009, H2087, A549	–	Up	ATAD3A, SAE2, CCDC66, EGFR	HGF/c-Met axis	Enhance LADC cell EMT and drug resistance	[176]
Circ-STXBP5L		–		Up	miR-224-3p and miR-512-3p	–	Circ-STXBP5L target miRNAs, causing LC progression	[177]
hsa_circ_0000064	–	A549, H1299	–	Up	Caspase-3, 9, BAX, p21, cyclin D1, CDK6, MMP-2, 9	–	Induces cancer cell proliferation, apoptosis and metastasis	[178]
Circ-FOXM1	80 NSCLC patients	H1299, A549, SK-MES-1, Calu-3HBE	–	Up	miR-1304-5p, PPDPF, MACC1	Circ-FOXM1/miR-1304-5p/PPDPF/MACC1 axis	Increases cellular growth and proliferation by sponging miR-1304-5p to target PPDPF and MACC1	[179]
Circ_0047921	patients (n = 60)	H1299, A549, H1650, Calu3, SK-MES1, BEAS-2B	Nude mice	Up	miR-1287-5p, LARP1	Circ_0047921/miR-1287-5p/LARP1 axis	Circ0047,921 serves as miR-1287-sponge, controlling LC cell proliferation, migration, and glycolysis	[180]
Circ-0006006	–	A549, H1299	Nude mice	–	miR-924, SRSF7	MiR-924/SRSF7 axis	Accelerated NSCLC development by regulation of SRSF7 expression via miR-924 sponging	[181]
Circ_0008717	48 NSCLC patients and 48 control samples	A549, H1299, BEAS-2B	Nude mice	High expression	miR-1287-5p, PAK2	miR-1287-5p/P21-mediated kinase 2 (PAK2) pathway	Promotes carcinogenesis in NSCLC by increasing expression of PAK2 via miR-1287-5p sponging	[182]
CircMAGI3	30 NSCLC patients	H322, H460, A549, H1299, NHBE	Nude mice	up	HDGF, miR-515-5p	CircMAGI3/miR-515-5p/HDGF pathway	Stimulates cell glycolysis and NSCLC cell proliferation	[183]
Circ-ABCB10	40 NSCLC patient samples	SPC-A1, HCC827, H1975, H1650, PC9, A549	Nude mice	up	MiR-584-5p, E2F5	MiR-584-5p/ E2F5 pathway	Participate in the upregulation of E2F5 expression by sponging miR-584-5p	[84]
hsa_circ_0062389	33 paired of NSCLC samples	H1650, H23, H522, A549, H1703, H460, BEAS-2B	–	up	MiR-103a-3p, CCNE1	MiR-103a-3p/CCNE1 axis	Utilize miR-103a-3p as a sponge to control CCNE1 expression in LC	[184]
Circ_0072088	20 patients with LUAD	H1299, H1975, H520, H827	–	Up	MiR-1261, PIK3CA	Circ_0072088/miR-1261/PIK3CA regulatory pathway	Tumorigenesis and progression of LUAD	[185]
Circ_0007385	–	–	Nude mice	Up	MiR-1253, FAM83A	MiR-1253/FAM83A axis	Promoted NSCLC cell proliferation and stemness	[186]
CircTUBA1C	30 pairs of LC tissue samples	Calu-3, A549	Nude mice	Up	MiR-143-3p, Cyclin B1, PCNA, BAX, caspase-3	CircTUBA1C/miR-143-3p axis	CircTUBA1C sponges miR-143-3p to promote NSCLC	[187]
Circ-PITX1	40 patients with primary NSCLC	H1975, A549, BEAS	Nude mice	Up	MiR-30e-5p, ITGA6	MiR-30e-5p/ITGA6 axis and ITGA6/PI3K/Akt pathway	MiRNA sponge	[188]
CircFECR1	35 moderate and 26 extensive SCLC patients	NCI-H460,NCI-H446, NCI-H2170,NCI-H1688, NCI-H1299, HCC-827	Nude mice	Up	MiR584-3p, ROCK1	MiR584–ROCK1 pathway	miR584-3p ensnared and deactivated by FECRs, which triggered the ROCK1 pathway	(189)
CircRNA-102481	58 NSCLC patients	PC9	–	Up	MiR-30a-5p sponge, ROR1	CircRNA_1024810/miR-30a-5p/ROR1 axis	promotes EGFR-TKI resistance through the miR-30a-5p/ROR1 pathway	[190]
CircSATB2	59 NSCLC and normal tissue samples	BEAS-2B, A549, H460, H1299, H226, MES-1	–	Up	MiR-326, FSCN1	–	Encourages LC to grow, spread, and invade	[191]
Hsa_circ_0002130	28 osimertinib-resistant LC (non-response) and 32 sensitive (response)	HCC827, H1975	Nude mice	Highly expressed	MiR-498, GLUT1, HK2, LDHA	–	Osimertinib-resistant NSCLC promotion	[192]
Circ_100876	–	A549, NCI-H23	–	Up	Targeting miR-636, RET	MiR-636/RET axis	CircRNA 100876 downregulation decreased NSCLC via the miR-636/RET pathway	[193]
Circ_0002346	45 NSCLC tissue specimens	HBE, A549, H1299	Nude mice	Up	miR-582-3p, STXBP6	miR-582-3p/STXBP6 pathway	Circ 0002346 sponges miR-582-3p to promote STXBP6 in NSCLC cells	[194]
Hsa_circ_0018818	30 pairs of LC and normal tissues	A549, NCI-H1650, PC-9, 293 T, NCI-H441, BEAS-2B	Nude mice	Up	miR-767-3p, NID1	miR-767-3p/NID1 signaling pathway	Targeted shRNA decreased NSCLC cell growth, invasion and induced the apoptosis process	[195]