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. 2021 Mar 1;2021:6659908. doi: 10.1155/2021/6659908

Table 1.

The evidence of regulatory roles of circRNAs in various diseases under oxidative stress.

Evidence from basic research
Cell line/animal Disease model/treatment Sample circRNA Alteration of expression Various roles in the pathophysiological mechanism Reference
HT22 cells OGD/R Cell mmu-circRNA-015947 Upregulated May participate in apoptosis-related, metabolism-related, and immune-related pathways [62]
CMVECs Oxidative stress induced by H2O2 Cell circHIPK3 Upregulated Overexpression significantly decreased apoptosis and protected CMVECs against H2O2-induced oxidative damages [78]
HUVECs Oxidative stress induced by HG Cell circBPTF Upregulated Regulate HG-induced HUVEC dysfunction, including apoptosis, inflammation, and oxidative stress [80]
SH-SY5Y cells Oxidative stress induced by H2O2 Cell circPRKCI Downregulated Alleviate the cytotoxicity induced by H2O2 [92]
ARPE-19 cells Oxidative stress induced by HG Cell circRNA_0084043 Upregulated May enhance malondialdehyde content and decrease activities of SOD and glutathione peroxidase, resulting in enhancing the oxidative stress in HG-indicated human retinal pigment epithelium ARPE-19 cells [102]
Rat Schwann RSC96 cells Oxidative stress induced by HG Cell circACR Downregulated Relieve the oxidative stress caused by HG [95]
Vascular smooth muscle cells Hyperglycemia stimulation Exosomes circRNA-0077930 (See the right column) Its overexpression increases the lactate dehydrogenase activity, reduces the antioxidative stress marker (SOD) activity, and induces senescence [82]
H9c2 cells 100 μM H2O2 treatment Cell circNCX1 Upregulated Lead to the death of cardiomyocytes in vitro and in vivo, acting as an endogenous miR-133a-3p sponge [101]
H9c2 cells Oxidative stress induced by H2O2 Cell circNFIX Downregulated Facilitates oxidative stress-induced H9c2 cells apoptosis [107]
Mesangial cells High glucose- (HG-) treated Cell circLRP6 Upregulated Regulates HG-induced proliferation, oxidative stress, ECM accumulation, and inflammation in mesangial cells via sponging miR-205, upregulating HMGB1, and activating TLR4/NF-κB pathway [108]
Rat ICH Cortical tissues around the hematoma rno_circRNA_011054
rno_circRNA_005098
rno_circRNA_012556		 Upregulated
Downregulated		 Promising targets for therapeutic intervention of ICH [58]
Chicken NH3 treatment Thymuses circRNA-SMC6 (See the right column) Correlated with OXR1, which can protect cells from oxidative damage [109]
Mouse Nrf2 knockout Substantia nigra mmu-circRNA-32463
mmu-circRNA-015216		 Upregulated
Downregulated		 A potential regulator of Nrf2-mediated neuroprotection against oxidative stress [88]
Mouse Nrf2 knockout Corpus striatum mmu-circRNA-017077 Downregulated Participate in Nrf2-mediated Fas-induced apoptosis in a variety of neurological diseases associated with oxidative stress [88]
Mouse tMCAO Cortical tissue circ_008018 Upregulated Result in brain tissue damage and neurological deficits [63]
Mouse Oxidative stress induced by H2O2 Cardiac endothelial cells circHIPK3 Enriched in exosomes Promote accelerated cell cycle progression and proliferation [79]
Mouse tMCAO Cell lysates circ_008018
circ_015350
circ_016128
circ_011137
circ_001729
circ_006696		 Upregulated
6 hours reperfusion after transient MCAO
Downregulated
6 hours reperfusion after transient MCAO		 Might have functional consequences in controlling the secondary brain damage and neurological dysfunction [57]
Mouse tMCAO Cell lysates circDLGAP4 Downregulated Decrease neurological deficits and infarct areas and blood-brain barrier (BBB) damage [60]
Mouse Diabetic retinopathy Cell lysates circZNF609 Upregulated Capillary degeneration and pathological angiogenesis [73]
Rat Coronary atherosclerosis Coronary artery tissue circANRIL In the empty vector and overexpressed cANRIL groups, atherosclerotic plaques and thrombi appeared Reduced cANRIL expression could prevent coronary AS by reducing vascular EC apoptosis and inflammatory factor expression [75, 76]
Mouse Hypertrophy and heart failure induced by ISO treatment Cardiomyocytes mm9_circ_012559, circHRCR Downregulated Inhibits cardiac hypertrophy and heart failure by targeting miR-223 and ARC [99]
Mouse MI Mouse myocardial tissues and mouse blood samples circCDR1 Upregulated May aggravate the oxidative stress in neuronal cells [94]
Rat Renal ischemia-reperfusion Mouse kidney tissues circAKT3 (See the right column) Involve RI/R injury progression through regulating miR-144-5p/Wnt/β-catenin pathway and oxidative stress [103]
Rats I/R pretreatment with salidroside Rat heart tissues circ_0000064 Upregulated Have a protective effect on myocardial ischemia-reperfusion injury [98]
Evidence from clinical research
Disease Sample Treatment circRNA Alteration of expression Various roles in the pathophysiological mechanism Reference
AIS Plasma from patients N/A circDLGAP4 Downregulated Decrease neurological deficits and infarct areas and blood-brain barrier (BBB) damage [60]
AIS Plasma from patients N/A circFUNDC1, circPDS5B, circCDC14A Upregulated Serve as biomarkers for AIS diagnosis and prediction of stroke outcomes [61]
Acute carotid-related cerebrovascular ischemia Plasma from patients N/A The ratio of circRNA-284/miR-221 Increased Detect plaque rupture and stroke, as biomarkers in cardiovascular disease [64]
Parkinson's disease Postmortem brain tissues from patients N/A circSLC8A1 Upregulated In oxidative stress, oxidation itself may increase the circulation of circSLC8A1 in neurons and reduce the expression of SLC8A1 protein [91]
Glioma In glioma tissues from patients and cells (T98G and LN229) N/A circSCAF11 Upregulated Its knockdown repressed cell proliferation and invasion [104]
Intestinal infarction In the intestinal mucosal tissues of mice and patients undergoing surgery for acute mesenteric arterial embolism, strangulated intestinal obstruction, or incarcerated hernia I/R circPRKCB Upregulated circPRKCB silencing or miR-339-5p overexpression significantly downregulated p66Shc expression and attenuated oxidative stress levels and I/R injury [105]
Atherosclerotic plaques SMCs and CD68-positive macrophages from patients N/A circANRIL Upregulated May alter RNA function and confer atheroprotection [9]
ARC Lens epithelial cells from patients N/A circHIPK3 Downregulated Under oxidative stress, circHIPK3 silencing increased the number of cell death and inhibited cell proliferation [77]
Human dental pulp stromal cells (a mesenchymal stromal cell source for regenerative therapy) Human dental pulp stromal cells Oxidative stress induced by H2O2 hsa_circ_0000257 Upregulated The hsa_circ_0000257/hsa-miR-9-5p/SIRT1/p53 regulatory axis is likely a novel molecular pathway regulating oxidative stress in hDPSCs [110]

Abbreviations: AIS: acute ischemic stroke; ARC: age-related cataract; CMVECs: cardiac microvascular endothelial cells; H2O2: hydrogen peroxide; HUVECs: human umbilical vein endothelial cells; ICH: intracerebral hemorrhage; I/R: ischemia-reperfusion; MI: myocardial infarction; Nrf2: nuclear factor erythroid 2-related factor 2; NH3: ammonia; HG: high glucose; OGD/R: oxygen-glucose deprivation/reoxygenation; SMCs: smooth muscle cells; SOD: superoxide dismutase; tMCAO: transient middle cerebral artery occlusion.