Introduction
Characteristics and biogenesis of circRNAs
Functional mechanisms of circRNAs
Act as miRNA sponges
Interact with RNA binding proteins
Regulate transcription or splicing
Translate proteins
Regulate epigenetic alterations
CircRNAs regulate the hallmarks of cancer
Function | CircRNA | Cancer type | expression | Associated clinical features | Associated cell process | Targets | Ref. |
---|---|---|---|---|---|---|---|
Sustaining growth signaling | CDR1as | NSCLC | up | TNM stage, lymph nodes metastasis and survival time | promote cell vitalities and growth, inhibit apoptosis and cell cycle arrest | miR-7/EGFR, CCNE1, PIK3CD. | [72] |
CDR1as | CRC | up | advanced tumor stage, tumor depth, and survival time | – | miR-7/EGFR, RAF1 | [73] | |
CDR1as | HCC | down | – | promote cell growth, adhesion, and inhibit migration | miR-7/EGFR | [74] | |
circHIPK3 | CRC | up | metastasis, clinical stage and survival time | inhibite cell proliferation, migration, invasion, and induce apoptosis | miR-7/EGFR, FAK, IGF1R, YY1 | [75] | |
hsa_circ_0046701 | glioma | up | – | promote cell proliferation and invasion | miR-142-3p/ITGB8 | [80] | |
circ-FBXW7 | glioblastoma | down | survival time | inhibit cell proliferation and cell cycle acceleration | FBXW7-185aa/c-Myc | [52] | |
Circ-Amotl1 | – | up | – | promote cell proliferation | c-myc | [84] | |
Evading growth inhibitors | circ-ITCH | Bca | down | histological grade and survival time | inhibite cell proliferation, migration, invasio, induce G1/S cell cycle arrest and apoptosis | miR-17, miR-224/p21, PTEN axis | [90] |
circ-ZFR | GC | down | – | inhibit cell propagation, cell cycle and promote apoptosis | miR-130a, miR-107/PTEN | [91] | |
CDR1as | GC | up | lymph nodes metastasis and survival time | promote cell proliferation, migration and inhibit apoptosis | miR-7/PTEN/PI3K/AKT | [92] | |
circRNA-000425 | GC | down | – | inhibit cell growth | miR-17,miR-106/p21, BIM | [93] | |
Circ100284 | – | up | – | promote cell cycle acceleration | miR-217/EZH2/cyclin D1, CDK4 | [97] | |
hsa_circ_0016788 | HCC | up | – | promote cell proliferation, invasion and inhibit apoptosis | miR-486/CDK4 axis | [98] | |
circHIPK3 | gallbladder cancer | up | – | promote cell survival and proliferation, inhibit cell apoptosis | miR-124/ROCK1, CDK6 | [99] | |
Resisting apoptosis | hsa_circ_0007534 | CRC | up | tumor stage and lymph node metastasis | ptomote cell proliferation and inhibit apoptosis | Bcl-2, Bax | [104] |
circUBAP2 | osteosarcoma | up | tumor progression and prognosis | promote cell growth and inhibit apoptosis | miR-143/Bcl-2 | [105] | |
hsa_circ_0009910 | osteosarcoma | up | – | promote cell proliferation inhibition, inhibit cell cycle arrest, and inhibit apoptosis | miR-449a/IL6R/Bcl-2/Bax | [106] | |
hsa_circRNA_103809 | CRC | down | – | promote apoptosis | miR-532-3p/FOXO4 axis | [107] | |
circNFIX | glima | up | – | promote cell propagation, migration and inhibit apoptosis | miR-34a-5p/NOTCH1 | [108] | |
circ-DNMT1 | BC | up | – | inhibit autophagy, promote cell proliferation and survival | p53, AUF1 | [110] | |
Uncontrolled replicative immortality | has-circ-0020397 | CRC | up | – | promote cell viability and inhibit apoptosis | mir-138/TERT, PD-L1 | [114] |
Promoting angiogenesis | circRNA-MYLK | Bca | up | pathological stage, T and N classifications and survival time | promote cell growth, angiogenesis and metastasis | miR-29a/VEGFA/VEGFR2 | [118] |
cZNF292 | Glima | up | – | promote cell proliferation, tube formation and angiogenic potential | VEGF-A, EGF, TGF-β1 | [122] | |
circHIPK3 | Bca | down | tumor grade, invasion, lymph node metastasis | inhibit migration, invasion, and angiogenesis | miR-558/HPSE/VEGF | [119] | |
Activating invasion and metastasis | circ-10,720 | HCC | up | Tumor metastasis and survival time | promote cell proliferation, migration, invasion and EMT | Vimentin | [129] |
circPTK2 | NSCLC | down | – | inhibit cell invasion and EMT | miR-429, miR-200b-3p/TIF1y | [132] | |
circSMAD2 | HCC | down | – | inhibit cell migration, invasion, and EMT | miR-629 | [137] | |
hsa_circ_0061140 | ovarian cancer | up | – | promote cell proliferation, migration, invasion and EMT | miR-370/FOXM1 | [141] | |
circ_0067934 | NSCLC | up | TNM stage, lymph node statu, distant metastasis and survival time | promote cell proliferation, migration, invasion and EMT | N-cadherin, vimentin snail, and E-cadherin | [142] | |
circRNA_0023642 | GC | up | – | pormote cell proliferation, migration, invasion and EMT | N-cadherin, vimentin snail, and E-cadherin | [143]` |
Self-sufficiency in growth signals
Insensitivity antigrowth signals
Evading apoptosis
Limitless replicative potential
Sustained angiogenesis
Tissue invasion and metastasis
CircRNAs regulate stemness of cancer
Function | CircRNA | Cancer type | expression | Associated clinical features | Associated cell process | Targets | Ref |
---|---|---|---|---|---|---|---|
Regulating stemness | circVRK1 | BC | down | – | decrease proportion of BCSCs with CD44 + CD24- phenotype, suppress BCSC’s expansion and self-renewal capacity | – | [147] |
hg19_circ_0005033 | LSCC | up | – | promote proliferation, migration, invasion, and chemotherapy resistance of laryngeal cancer stem cells | miR-4521 | [150] | |
Regulating chemotherapy resistance | circPVT1 | osteosarcoma | up | enneking stage, chemoresistance, lung metastasis and survival | contributes to doxorubicin and cisplatinresistance | ABCB1 | [154] |
circRNA-MTO1 (hsa-circRNA-007874) | BC | up | – | inhibit cell viability and reverse monastrol resistance | TRAF4/Eg5 axis | [157] | |
circBA9.3 | CML | up | – | promote resistance against TKI therapy | c-ABL1 and BCR-ABL1 | [159] |
CircRNAs regulate chemotherapy resistance of cancer
CircRNAs as biomarkers in Cancer
Source | Cancer type | Cohort size | CircRNA | Expression | Associated clinical features | Ref |
---|---|---|---|---|---|---|
saliva | OSCC | 90 OSCC patients, 70 OLK subjects | hsa_circ_0001874 | up | TNM stage, tumor grade | [165] |
OSCC | 90 OSCC patients, 70 OLK subjects | hsa_circ_0001971 | up | TNM stage | [165] | |
plasma | GC | 104 GC patients, 104 healthy individuals | Hsa_circ_0000190 | down | tumor diameter, lymphatic metastasis, distal metastasis, TNM stage, CA19–9levels | [163] |
GC | 20 GC patients, 20 healthy individuals | hsa_circ_0006633 | up | distal metastasis, tissue carcinoembryonic antigen level | [167] | |
GC | 45 GC patients, 17 healthy individuals | hsa_circ_0000520 | down | CEA expression | [168] | |
GC | 24 GC patients, 14 healthy individuals | hsa_circ_0000673 | down | TNM stage | [169] | |
GC | 121 GC patients, 121 healthy individuals | hsa_circ_0001017, hsa_circ_0061276 | down | OS, DFS | [170] | |
ESCC | 30 ESCC patients, 25 healthy individuals | Circ-TTC17 | up | TNM stage, lymphatic metastasis, OS | [171] | |
PC | 31 PC patients, 31 healthy individuals | circ-LDLRAD3 | up | CA19–9, N classification, venous invasion, lymphatic invasion | [172] | |
BC | 57 BC patients, 17 healthy individuals | hsa_circ_0001785 | down | histological grade, TNM stage, distant metastasis | [173] | |
HCC | 104 HCC patients, 52 healthy individuals | hsa_circ_0001445 | down | AFP level | [174] | |
GC | 102 GC patients, 105 healthy individuals | Hsa_circ_0000181 | down | tumor differentiation, carcinoembryonic antigen | [175] | |
LAC | 30 LAC patients, 30 healthy individuals | hsa_circ_0013958 | up | TNM stage, lymphatic metastasis | [176] | |
serum | HCC | 64 HCC patients, 30 healthy individuals | circ-ZEB1.33 | up | TMN stages, OS | [162] |
BCa | 197 BCa patients, 97 healthy individuals | hsa_circ_0000285 | down | tumor size, differentiation, lymph node metastasis, distant metastasis, TNM stage, OS | [177] | |
NPC | 150 NPC patients, 100 healthy individuals | circRNA_0000285 | up | tumor size, differentiation, lymph node metastasis, distant metastasis, TNM stage. | [178] | |
exosome (serum and urine) | UCB | 71 UCB patients, 36 healthy individuals | circPRMT5 | up | lymph node metastasis, T and N status, DFS | [166] |
UCB | 18 UCB patients, 14 healthy individuals | circPRMT5 | up | lymph node metastasis, T and N status, DFS | [166] |