Circular RNAs in Ischemic Stroke: Biological Role and Experimental Models

Ischemic stroke is among the leading causes of morbidity, disability, and mortality worldwide. Despite the recent progress in the management of acute ischemic stroke, timely intervention still represents a challenge. Hence, strategies to counteract ischemic brain injury during and around the acute event are still lacking, also due to the limited knowledge of the underlying mechanisms. Despite the increasing understanding of the complex pathophysiology underlying ischemic brain injury, some relevant pieces of information are still required, particularly regarding the fine modulation of biological processes. In this context, there is emerging evidence that the modulation of circular RNAs, a class of highly conserved non-coding RNA with a closed-loop structure, are involved in pathophysiological processes behind ischemic stroke, unveiling a number of potential therapeutic targets and possible clinical biomarkers. This paper aims to provide a comprehensive overview of experimental studies on the role of circular RNAs in ischemic stroke.

[1]  Tian Yuan,et al.  Circ_0101874 overexpression strengthens PDE4D expression by targeting miR-335-5p to promote neuronal injury in ischemic stroke. , 2022, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[2]  Jinbo He,et al.  Circ_TLK1 knockdown alleviates oxygen–glucose deprivation/reoxygenation‐induced PC12 cell injury by regulating microRNA‐136‐5p/follistatin like‐1 axis , 2022, The European journal of neuroscience.

[3]  Youjie Zeng,et al.  Integrated Analysis of Immune-Related circRNA-miRNA-mRNA Regulatory Network in Ischemic Stroke , 2022, Frontiers in Neurology.

[4]  Lihua Dong,et al.  circHIPK3 regulates apoptosis and mitochondrial dysfunction induced by ischemic stroke in mice by sponging miR-148b-3p via CDK5R1/SIRT1 , 2022, Experimental Neurology.

[5]  A. Członkowska,et al.  Diagnostic Performance of Circulating miRNAs and Extracellular Vesicles in Acute Ischemic Stroke , 2022, International journal of molecular sciences.

[6]  Kai Sun,et al.  Impact of CircRNAs on Ischemic Stroke , 2022, Aging and disease.

[7]  Yan Gao,et al.  Overexpressing circ_0000831 is sufficient to inhibit neuroinflammation and vertigo in cerebral ischemia through a miR-16-5p-dependent mechanism , 2022, Experimental Neurology.

[8]  Yuanqiang Dai,et al.  Circ_0000647 promotes cell injury by modulating miR-126-5p/TRAF3 axis in oxygen-glucose deprivation and reperfusion-induced SK-N-SH cell model. , 2022, International immunopharmacology.

[9]  C. Tsang,et al.  CircOGDH Is a Penumbra Biomarker and Therapeutic Target in Acute Ischemic Stroke , 2022, Circulation research.

[10]  Hong Zhang,et al.  Circular noncoding RNA circ_0007865, serves as a competing endogenous RNA, targeting the miR-214-3p/FKBP5 axis to regulate oxygen-glucose deprivation-induced injury in brain microvascular endothelial cells , 2022, Neuroreport.

[11]  Jianping Zhang,et al.  Knockdown of circular RNA tousled-like kinase 1 relieves ischemic stroke in middle cerebral artery occlusion mice and oxygen-glucose deprivation and reoxygenation-induced N2a cell damage , 2022, Bioengineered.

[12]  Han Xiao,et al.  Knockdown of circHECTD1 inhibits oxygen-glucose deprivation and reperfusion induced endothelial-mesenchymal transition , 2022, Metabolic Brain Disease.

[13]  Xiang Ren,et al.  Knockdown of circRNA-Memo1 Reduces Hypoxia/Reoxygenation Injury in Human Brain Endothelial Cells Through miRNA-17-5p/SOS1 Axis , 2022, Molecular Neurobiology.

[14]  Dan Wang,et al.  Knockdown of circ_0007290 alleviates oxygen-glucose deprivation-induced neuronal injury by regulating miR-496/PDCD4 axis , 2022, Metabolic Brain Disease.

[15]  H. Huo,et al.  Silencing of circCDC14A prevents cerebral ischemia‐reperfusion injury via miR‐23a‐3p/CXCL12 axis , 2022, Journal of biochemical and molecular toxicology.

[16]  C. Indolfi,et al.  Flow-Responsive Noncoding RNAs in the Vascular System: Basic Mechanisms for the Clinician , 2022, Journal of clinical medicine.

[17]  Shuangxing Hou,et al.  Exosomes from hypoxic pre-treated ADSCs attenuate acute ischemic stroke-induced brain injury via delivery of circ-Rps5 and promote M2 microglia/macrophage polarization , 2021, Neuroscience Letters.

[18]  Xi Liu,et al.  CircFUNDC1 knockdown alleviates oxygen-glucose deprivation-induced human brain microvascular endothelial cell injuries by inhibiting PTEN via miR-375 , 2021, Neuroscience Letters.

[19]  J. Palatini,et al.  Altered Circulating MicroRNA Profiles After Endurance Training: A Cohort Study of Ultramarathon Runners , 2022, Frontiers in Physiology.

[20]  Zhijun Zhang,et al.  Down-regulation of circular RNA CDC14A peripherally ameliorates brain injury in acute phase of ischemic stroke , 2021, Journal of neuroinflammation.

[21]  S. Gan,et al.  Deep Sequencing of the Rat MCAO Cortexes Reveals Crucial circRNAs Involved in Early Stroke Events and Their Regulatory Networks , 2021, Neural plasticity.

[22]  S. Limborska,et al.  Genome-Wide RNA-Sequencing Reveals Massive Circular RNA Expression Changes of the Neurotransmission Genes in the Rat Brain after Ischemia–Reperfusion , 2021, Genes.

[23]  Xiu-ying Li,et al.  Circular RNA circPHKA2 Relieves OGD-Induced Human Brain Microvascular Endothelial Cell Injuries through Competitively Binding miR-574-5p to Modulate SOD2 , 2021, Oxidative medicine and cellular longevity.

[24]  Xiaohui Xu,et al.  CircDLGAP4 overexpression relieves oxygen-glucose deprivation-induced neuronal injury by elevating NEGR1 through sponging miR-503-3p , 2021, Journal of Molecular Histology.

[25]  Chen Chen,et al.  Circular RNA circLIFR regulates the proliferation, migration, invasion and apoptosis of human vascular smooth muscle cells via the miR-1299/KDR axis , 2021, Metabolic Brain Disease.

[26]  Yuanli Zhao,et al.  Circular RNA 0025984 Ameliorates Ischemic Stroke Injury and Protects Astrocytes Through miR-143-3p/TET1/ORP150 Pathway , 2021, Molecular Neurobiology.

[27]  S. De Rosa,et al.  Alterations in Circulating MicroRNAs and the Relation of MicroRNAs to Maximal Oxygen Consumption and Intima–Media Thickness in Ultra-Marathon Runners , 2021, International journal of environmental research and public health.

[28]  Vishal Chavda,et al.  PiWi RNA in Neurodevelopment and Neurodegenerative disorders. , 2021, Current molecular pharmacology.

[29]  Zhi Wang,et al.  Circ_0006768 upregulation attenuates oxygen–glucose deprivation/reoxygenation-induced human brain microvascular endothelial cell injuries by upregulating VEZF1 via miR-222-3p inhibition , 2021, Metabolic Brain Disease.

[30]  S. De Rosa,et al.  MiR-126 Is an Independent Predictor of Long-Term All-Cause Mortality in Patients with Type 2 Diabetes Mellitus , 2021, Journal of clinical medicine.

[31]  Zhen-duo Zhang,et al.  Circular RNA circ_HECTD1 regulates cell injury after cerebral infarction by miR-27a-3p/FSTL1 axis , 2021, Cell cycle.

[32]  Vishal Chavda,et al.  Coding and non-coding nucleotides': The future of stroke gene therapeutics. , 2021, Genomics.

[33]  Y. Wen,et al.  circRNA-0006896-miR1264-DNMT1 axis plays an important role in carotid plaque destabilization by regulating the behavior of endothelial cells in atherosclerosis , 2021, Molecular medicine reports.

[34]  H. Sourij,et al.  MicroRNAs and long non-coding RNAs in the pathophysiological processes of diabetic cardiomyopathy: emerging biomarkers and potential therapeutics , 2021, Cardiovascular Diabetology.

[35]  Zhenhang Chen,et al.  Identification of Differently Expressed mRNAs in Atherosclerosis Reveals CDK6 Is Regulated by circHIPK3/miR-637 Axis and Promotes Cell Growth in Human Vascular Smooth Muscle Cells , 2021, Frontiers in Genetics.

[36]  Bo Yang,et al.  Circular RNA TTC3 regulates cerebral ischemia-reperfusion injury and neural stem cells by miR-372-3p/TLR4 axis in cerebral infarction , 2021, Stem cell research & therapy.

[37]  M. Ghanbari,et al.  Circulatory MicroRNAs as Potential Biomarkers for Stroke Risk , 2021, Stroke.

[38]  Xu Liu,et al.  Inflammation-Related circRNA Polymorphism and Ischemic Stroke Prognosis , 2021, Journal of Molecular Neuroscience.

[39]  Xiaonan Xu,et al.  Circular RNA circPHC3 Promotes Cell Death and Apoptosis in Human BMECs After Oxygen Glucose Deprivation via miR-455-5p/TRAF3 Axis in vitro , 2021, Neuropsychiatric disease and treatment.

[40]  Yitao He,et al.  The functions of fluoxetine and identification of fluoxetine-mediated circular RNAs and messenger RNAs in cerebral ischemic stroke , 2021, Bioengineered.

[41]  Xiu-Miao Li,et al.  Retina as a window to cerebral dysfunction following studies with circRNA signature during neurodegeneration , 2021, Theranostics.

[42]  S. De Rosa,et al.  MicroRNAs and Long Noncoding RNAs in Coronary Artery Disease: New and Potential Therapeutic Targets. , 2020, Cardiology clinics.

[43]  Zhibiao Chen,et al.  Circular RNA circCCDC9 alleviates ischaemic stroke ischaemia/reperfusion injury via the Notch pathway , 2020, Journal of cellular and molecular medicine.

[44]  Hong Yang,et al.  Downregulation of circular RNA HECTD1 induces neuroprotection against ischemic stroke through the microRNA-133b/TRAF3 pathway. , 2020, Life sciences.

[45]  Lukui Chen,et al.  Overexpression of circRNA circUCK2 Attenuates Cell Apoptosis in Cerebral Ischemia-Reperfusion Injury via miR-125b-5p/GDF11 Signaling , 2020, Molecular therapy. Nucleic acids.

[46]  Lukui Chen,et al.  Exosome-Shuttled circSHOC2 from IPASs Regulates Neuronal Autophagy and Ameliorates Ischemic Brain Injury via the miR-7670-3p/SIRT1 Axis , 2020, Molecular therapy. Nucleic acids.

[47]  Fangming Li,et al.  Altered circular RNA expression profiles in the non-ischemic thalamus in focal cortical infarction mice , 2020, Aging.

[48]  Shengnan Guo,et al.  The regulated profile of noncoding RNAs associated with inflammation by tanshinone IIA on atherosclerosis , 2020, Journal of leukocyte biology.

[49]  Hui Zhang,et al.  Circ-camk4 involved in cerebral ischemia/reperfusion induced neuronal injury , 2020, Scientific Reports.

[50]  Li Yang,et al.  Extracellular Vesicle–Mediated Delivery of Circular RNA SCMH1 Promotes Functional Recovery in Rodent and Nonhuman Primate Ischemic Stroke Models , 2020, Circulation.

[51]  Y. Zhao,et al.  The decreased circular RNA hsa_circ_0072309 promotes cell apoptosis of ischemic stroke by sponging miR-100. , 2020, European review for medical and pharmacological sciences.

[52]  Eric S. Ho,et al.  Identification of Blood Circular RNAs as Potential Biomarkers for Acute Ischemic Stroke , 2020, Frontiers in Neuroscience.

[53]  F. Zang,et al.  Silencing of circular RNA HIPK2 in neural stem cells enhances functional recovery following ischaemic stroke , 2020, EBioMedicine.

[54]  Shijian Luo,et al.  Circ_016719 plays a critical role in neuron cell apoptosis induced by I/R via targeting miR-29c/Map2k6. , 2019, Molecular and cellular probes.

[55]  D. Peng,et al.  Identification and functional analysis of circular RNAs induced in rats by middle cerebral artery occlusion. , 2019, Gene.

[56]  Hyun Joon Lee,et al.  Current strategies for therapeutic drug delivery after traumatic CNS injury. , 2019, Therapeutic delivery.

[57]  C. Indolfi,et al.  Non-coding RNAs in vascular remodeling and restenosis. , 2019, Vascular pharmacology.

[58]  Yuan Zhang,et al.  Novel insight into circular RNA HECTD1 in astrocyte activation via autophagy by targeting MIR142-TIPARP: implications for cerebral ischemic stroke , 2018, Autophagy.

[59]  A. Curcio,et al.  Transcoronary concentration gradients of circulating microRNAs in heart failure , 2018, European journal of heart failure.

[60]  C. Indolfi,et al.  The Potential Role of Platelet-Related microRNAs in the Development of Cardiovascular Events in High-Risk Populations, Including Diabetic Patients: A Review , 2018, Front. Endocrinol..

[61]  Bing Han,et al.  Circular RNA DLGAP4 Ameliorates Ischemic Stroke Outcomes by Targeting miR-143 to Regulate Endothelial-Mesenchymal Transition Associated with Blood–Brain Barrier Integrity , 2018, The Journal of Neuroscience.

[62]  R. Vemuganti,et al.  Circular RNA Expression Profiles Alter Significantly in Mouse Brain After Transient Focal Ischemia , 2017, Stroke.

[63]  C. Indolfi,et al.  Modulation of Circulating MicroRNAs Levels during the Switch from Clopidogrel to Ticagrelor , 2016, BioMed research international.

[64]  Shan Ye,et al.  Circular RNA expression alterations are involved in OGD/R-induced neuron injury. , 2016, Biochemical and biophysical research communications.

[65]  C. Indolfi,et al.  Exosomal miRNAs in Heart Disease. , 2016, Physiology.

[66]  Paul M. George,et al.  Novel Stroke Therapeutics: Unraveling Stroke Pathophysiology and Its Impact on Clinical Treatments , 2015, Neuron.

[67]  G. Yousef,et al.  MicroRNAs as biomarkers in pituitary tumors. , 2014, Neurosurgery.

[68]  A. Curcio,et al.  Emerging role of microRNAs in cardiovascular diseases. , 2014, Circulation journal : official journal of the Japanese Circulation Society.

[69]  Trinachartvanit,et al.  Novel , 2002, English and American Studies in German.