Table 1.
The evidence of CircRNA regulatory roles in the pathophysiological changes of ischemic stroke.
| Pathological process in IS | Cell line/treatment | Animal/disease model | DE CircRNA and expression | Regulating axis | Overexpression role | References | |
|---|---|---|---|---|---|---|---|
| Evidences from basic research | |||||||
| Apoptosis | Arterial SMCs, HEK-293, iPSC | / | Circ_ANRIL | Up | PES1 | Induce apoptosis | (28) |
| Transfection of siRNA | Detrimental | ||||||
| HCtAECs and THP-1 cells | / | Circ_0003204 | Up | MiR-188-3p/TRPC6 | Induce apoptosis | (29) | |
| Ox-LDL | Detrimental | ||||||
| HUVECs | / | Circ_0003204 | Up | MiR-942-5p/HDAC9 | Induce apoptosis | (30) | |
| Ox-LDL | Detrimental | ||||||
| HUVECs | / | Circ_0003204 | Up | MiR-491-5p/ICAM1 | Induce apoptosis | (31) | |
| Ox-LDL | Detrimental | ||||||
| HUVECs | / | Circ_0003204 | Up | MiR-197-3p/ROBO1 | Induce apoptosis | (32) | |
| Ox-LDL | Detrimental | ||||||
| HUVECs | / | Circ_0003204 | Up | Unknown | Induce apoptosis | (33) | |
| Ox-LDL | Detrimental | ||||||
| HBMEC-IM cells | / | Circ_0003423 | Down | MiR-589-5p/TET2 | Inhibit apoptosis | (34) | |
| Ox-LDL | Protective | ||||||
| HUVECs | / | Circ_0003423 | Down | MiR-142-3p/Sirtuin 3, SOD2 | Inhibit apoptosis | (35) | |
| Ox-LDL | Protective | ||||||
| mAS | Mouse | CircCTNNB1 | Down | MiR-96-5p/SRB1 | Inhibit apoptosis | (36) | |
| OGD/R | MCAO | Protective | |||||
| HBMECs | / | CircPHKA2 | Down | MiR-574-5p/SOD2 | Inhibit apoptosis | (37) | |
| OGD | Protective | ||||||
| SK-N-SH | / | Circ_0000647 | Up | MiR-126-5p/TRAF3 | Induce apoptosis | (38) | |
| OGD/R | Detrimental | ||||||
| HBMVECs | / | Circ-Memo1 | Up | MiR-17-5p/SOS1 | Induce apoptosis | (39) | |
| H/R | Detrimental | ||||||
| Apoptosis | HCN-2 | / | CircDlgap4 | Down | MiR-503-3p/NEGR1 | Inhibit apoptosis | (40) |
| OGD | Protective | ||||||
| HUVECs | Mouse | CircDlgap4 | Down | MiR-143/HECTD1 | Inhibit apoptosis | (41) | |
| I/R | I/R | Protective | |||||
| Astrocytes | Rats | Circ 0025984 | Down | MiR-143-3p/TET1/ORP150 | Inhibit apoptosis | (22) | |
| OGD | MCAO | Protective | |||||
| Brain-derived endothelial cells | Mouse | Circ_0072309 | Down | MiR-100/mTOR | Inhibit apoptosis | (42) | |
| OGD | MCAO | Protective | |||||
| HT22 cells | Mouse | CircCDC14A | Up | MiR-23a-3p/CXCL12 | Induce apoptosis | (43) | |
| OGD/R | MCAO | Detrimental | |||||
| HBMECs | / | CircFUNDC1 | Up | MiR-375/PTEN | Induce apoptosis | (44) | |
| OGD | Detrimental | ||||||
| HBMECs | / | CircPHC3 | Up | MiR-455-5p/TRAF3 | Induce apoptosis | (45) | |
| OGD | Detrimental | ||||||
| RGCs | Mouse | CGLIS3 | Up | MiR-203/unknown | Induce apoptosis | (46) | |
| OGD/R | tMCAO | Detrimental | |||||
| HT22 cells | Mouse | Circ-HECTD1 | Up | MicroRNA-133b/TRAF3 | Inhibit apoptosis | (47) | |
| OGD | MCAO | Protective | |||||
| HT22 cells | Mouse | Circ-HECTD1 | Up | MiR-27a-3p/FSTL1 | Inhibit apoptosis | (48) | |
| OGD/R | MCAO | Protective | |||||
| / | Mouse | Circ_008018 | Up | MiR-99a/Akt, GSK3β | Induce apoptosis | (49) | |
| MCAO | Detrimental | ||||||
| Astrocytes | Mouse | CircTTC3 | Up | MiR-372-3p/TLR4 | Induce apoptosis | (50) | |
| OGD | MCAO/R | Detrimental | |||||
| Oxidative Stress | mAS | Mouse | CircCTNNB1 | Down | MiR-96-5p/SRB1 | Inhibit oxidative stress | (36) |
| OGD/R | MCAO | Protective | |||||
| HBMECs | / | CircPHKA2 | Down | MiR-574-5p/SOD2 | Inhibit oxidative stress | (37) | |
| OGD | Protective | ||||||
| SK-N-SH | / | Circ_0000647 | Up | MiR-126-5p/TRAF3 | Induce oxidative stress | (38) | |
| OGD/R | Detrimental | ||||||
| Oxidative Stress | HBMVECs | / | Circ-Memo1 | Up | MiR-17-5p/SOS1 | Induce oxidative stress | (39) |
| H/R | Detrimental | ||||||
| HCtAECs and THP-1 cells | / | Circ_0003204 | Up | MiR-188-3p/TRPC6 | Induce oxidative stress | (29) | |
| Ox-LDL | Detrimental | ||||||
| N2a cells, neurons | Mouse | CircDlgap4 | Down | AUF1/NRF2 mRNA | Inhibit oxidative stress | (51) | |
| OGD | tMCAO | Protective | |||||
| Inflammation | HBMECs | / | Circ_ANRIL | Up | MiR-622 | Induce inflammation | (52) |
| OGD/R | Detrimental | ||||||
| HCtAECs and THP-1 cells | / | Circ_0003204 | Up | MiR-188-3p/TRPC6 | Induce inflammation | (29) | |
| Ox-LDL | Detrimental | ||||||
| HUVECs | / | Circ_0003204 | Up | MiR-942-5p/HDAC9 | Induce inflammation | (30) | |
| Ox-LDL | Detrimental | ||||||
| HUVECs | / | Circ_0003204 | Up | MiR-491-5p/ICAM1 | Induce inflammation | (31) | |
| Ox-LDL | Detrimental | ||||||
| HUVECs | / | Circ_0003204 | Up | MiR-197-3p/ROBO1 | Induce inflammation | (32) | |
| Ox-LDL | Detrimental | ||||||
| mAS | Mouse | CircCTNNB1 | Down | MiR-96-5p/SRB1 | Inhibit inflammation | (36) | |
| OGD/R | MCAO | Protective | |||||
| SK-N-SH | / | Circ_0000647 | Up | MiR-126-5p/TRAF3 | Induce inflammation | (38) | |
| OGD/R | Detrimental | ||||||
| HBMVECs | / | Circ-Memo1 | Up | MiR-17-5p/SOS1 | Induce inflammation | (39) | |
| H/R | Detrimental | ||||||
| HCN-2 | / | CircDlgap4 | Down | MiR-503-3p/NEGR1 | Inhibit inflammation | (40) | |
| OGD | Protective | ||||||
| HBMECs | / | Circ_0006768 | Down | MiR-222-3p/VEZF1 | Inhibit inflammation | (53) | |
| OGD/R | Protective | ||||||
| Angiogenesis | HBMEC-IMs | / | Circ_0003423 | Down | MiR-589-5p/TET2 | Promote angiogenesis | (34) |
| Ox-LDL | Protective | ||||||
| HUVECs | / | Circ_0003423 | Down | MiR-142-3p/Sirtuin 3, SOD2 | Promote angiogenesis | (35) | |
| OGD | Protective | ||||||
| Angiogenesis | HBMECs | / | Circ_0006768 | Down | MiR-222-3p/VEZF1 | Promote angiogenesis | (53) |
| OGD/R | Protective | ||||||
| HBMECs | / | CircFUNDC1 | Up | MiR-375/PTEN | Inhibit angiogenesis | (44) | |
| OGD | Detrimental | ||||||
| HUVECs | / | Circ_0003204 | Up | Unknown | Inhibit angiogenesis Detrimental | (33) | |
| Ox-LDL | |||||||
| HBMEC | / | CircPHKA2 | Down | MiR-574-5p/SOD2 | Promote angiogenesis | (37) | |
| OGD | Protective | ||||||
| Autophagy | Astrocytes, A172cells | Mouse | CircHECTD1 | Up | MiR142/TIPARP | Promote autophagy Detrimental | (25) |
| OGD-R | tMCAO | ||||||
| Astrocytes | Mouse | CircSHOC2 | Up | MiR-7670-3p/SIRT1 | Inhibit autophagy | (24) | |
| OGD | MCAO | Protective | |||||
| A172 and SK-N-AS | Mouse | Circ_0025984 | Down | MiR-143-3p/TET1 | Inhibit autophagy | (22) | |
| OGD | MCAO | Protective | |||||
| BEnd.3 or HBMECs | Mouse | Circ-FoxO3 | Up | MTOR and E2F1 | Promote autophagy | (23) | |
| OGD/R | MCAO/R | Protective | |||||
| HT22 cells | Mouse | Circ_016719 | Up | MiR-29c/Map2k6 | Promote autophagy | (26) | |
| OGD/R | tMCAO | Detrimental | |||||
| Astrocytes | Mouse | CircAkap7 | Down | MiR-155-5p/ATG12, NRF2 | Promote autophagy | (27) | |
| OGD/R | tMCAO | Protective | |||||
| Other way | HASMCs, MASMCs | / | Circ_ACTA2 | Up | MiR-548f-5p/α-SMA | Facilitate stress fiber formation and cell contraction | (54) |
| Detrimental | |||||||
| Astrocytes, microglia | / | CircSCMH1 | Down | MeCP2 | Enhance neuronal plasticity, inhibit glial activation and peripheral immune cell infiltration | (55) | |
| OGD | Protective | ||||||
| NSCs | Mouse | CircHIPK2 | Up | Smox | Reduce neuronal differentiation | (56) | |
| OGD/R | tMCAO | Detrimental | |||||
PES1, Pescadillo homolog 1; TRPC6, transient receptor potential canonical channel 6; HDAC9, histone deacetylase 9; HUVECs, human umbilical vein endothelial cells; ICAM1, intercellular adhesion molecule 1; ROBO1, roundabout guidance receptor 1; ox-LDL, oxidized low-density lipoprotein; TET2, ten-eleven translocation 2; HBMECs, human brain microvascular endothelial cells; SOD2, superoxide dismutase 2; mAS, mouse astrocytes; OGD/R, oxygen and glucose deprivation/reoxygenation; MCAO, middle cerebral artery occlusion; SRB1, scavenger receptor class B type 1; OGD, oxygen and glucose deprivation; TRAF3, tumor necrosis factor receptor-associated factor 3; HBMVECs, human brain microvascular endothelial cells; H/R, hypoxia/reoxygenation; SOS1, Son of Sevenless 1; NEGR1, neuronal growth regulator 1; I/R, ischemia/reperfusion; TET1, ten-eleven translocation methylcytosine dioxygenase 1; ORP150, oxygen-regulated protein 150; mTOR, mechanistic target of rapamycin; CXCL12, C-X-C motif chemokine 12; PTEN, phosphatase and tensin homolog; FSTL1, follistatin-like 1; Akt, protein kinase B; GSK3β, glycogen synthase kinase 3β; TLR4, Toll-like receptor 4; TRPC6, transient receptor potential canonical channel 6; tMCAO, transient middle cerebral artery occlusion; NRF2, nuclear factor erythroid 2-related factor 2; HDAC9, histone deacetylase 9; ICAM1, intercellular adhesion molecule 1; NEGR1, neuronal growth regulator 1; VEZF1, vascular endothelial zinc finger 1; SIRT3, sirtuin 3; TIPARP, TCDD inducible poly(ADP-ribose) polymerase; SIRT1, sirtuin 1; E2F1, E2F transcription factor 1; Map2k6, Rac-MAPK kinase 6; ATG12, autophagy-related genes 12; HASMCs, human aortic smooth muscle cells; MASMCs, mouse aortic vascular smooth muscle cells; α-SMA, smooth muscle α-actin; MeCP2, methyl-CpG binding protein 2; Smox, spermine oxidase; SK-N-SH, Human neuroblastoma cell line; H/R, hypoxia/reoxygenation; HCN-2, human cortical neuronal cells-2; RGCs, retinal ganglion cells; HCtAECs, human carotid artery endothelial cells; NSCs, neural stem cells.