Table 1 Oncogenic exo-circRNAs and their role in lung cancer

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]