Novel Insights Toward Human Stroke-Related Epigenetics: Circular RNA and its Impact in Poststroke Processes

Silva, Pablo W; Shimon, Samara M M; Brito, Leonardo Miranda; Reis-das-Mercês, Laís; Magalhães, Leandro; Araújo, Gilderlanio Santana de; Ribeiro-dos-Santos, Ândrea; Vidal, Amanda Ferreira

doi:10.2217/epi-2020-0128

Cited by 11 publications

(6 citation statements)

References 27 publications

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“…The China Stroke Prevention Project Committee (CSPPC) established in 2011 intends to promote stroke prevention and control and improve stroke care [2]. Pathophysiologically, cerebral ischemia causes a sequence of detrimental events, including inflammation, oxidative stress, endoplasmic reticulum (ER) stress, and apoptosis [3], as well as alteration of epigenetics [4,5]. New pharmacological interventions, including noncoding RNA-(ncRNA-) based strategies, have shown promise for treatment of AIS.…”

Section: Introductionmentioning

confidence: 99%

“…Circular RNAs (circRNAs) are an evolutionarily conserved class of ncRNAs that are formed in a circular conformation via noncanonical splicing or backsplicing events [6]. Global expression of circRNAs is differentially altered in ischemic lesion tissue, peripheral blood, and peripheral blood mononuclear cell from AIS patients [4,7,8]. Circular RNAs are broadly involved in stroke-related neurovascular damages [9], and thus, circRNAs are proposed as novel diagnostic and prognostic biomarkers for AIS [7,10].…”

Section: Introductionmentioning

confidence: 99%

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Circular RNA circPHKA2 Relieves OGD‐Induced Human Brain Microvascular Endothelial Cell Injuries through Competitively Binding miR‐574‐5p to Modulate SOD2

Yang

Zhong

et al. 2021

Oxidative Medicine and Cellular Longevity

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Background. Circular RNA phosphorylase kinase regulatory subunit alpha 2 (circPHKA2; hsa_circ_0090002) has a significantly, specifically different expression in acute ischemic stroke (AIS) patients’ blood. Here, we intended to investigate the role and mechanism of circPHKA2 in oxygen-glucose deprivation- (OGD-) induced stoke model in human brain microvascular endothelial cells (HBMEC). Methods. Expression of circPHKA2, microRNA- (miR-) 574-5p, and superoxide dismutase-2 (SOD2) was detected by quantitative PCR and western blotting. Cell injury was measured by detecting cell proliferation (EdU assay and CCK-8 assay), migration (transwell assay), neovascularization (tube formation assay), apoptosis (flow cytometry and western blotting), endoplasmic reticulum stress (western blotting), and oxidative stress (assay kits). Direct intermolecular interaction was determined by bioinformatics algorithms, dual-luciferase reporter assay, biotin-labelled miRNA capture, and argonaute 2 RNA immunoprecipitation. Results. circPHKA2 was downregulated in AIS patients’ blood in SOD2-correlated manner. Reexpressing circPHKA2 rescued EdU incorporation, cell viability and migration, tube formation, B cell lymphoma-2 (Bcl-2) expression, and SOD activity of OGD-induced HBMEC and alleviate apoptotic rate and levels of Bcl-2-associated protein (Bax), glucose-regulated protein 78 kD (GRP78), C/EBP-homologous protein (CHOP), caspase-12, reactive oxygen species (ROS), and malondialdehyde (MDA). Additionally, blocking SOD2 partially attenuated these roles of circPHKA2 overexpression. Molecularly, circPHKA2 upregulated SOD2 expression via interacting with miR-574-5p, and miR-574-5p could target SOD2. Similarly, allied to neurovascular protection of circPHKA2 was the downregulation of miR-574-5p. Conclusion. circPHKA2 could protect HBMEC against OGD-induced cerebral stroke model via the miR-574-5p/SOD2 axis, suggesting circPHKA2 as a novel and promising candidate in ischemic brain injury.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Circular RNA circPHKA2 Relieves OGD‐Induced Human Brain Microvascular Endothelial Cell Injuries through Competitively Binding miR‐574‐5p to Modulate SOD2

Yang

Zhong

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…Cerebral ischemia causes a complex sequence of events, including neuroinflammation, reactive oxygen species, mitochondria dysregulations, impairment in neurotransmission, apoptosis, as well as epigenetic alterations [18]. Plasma biomarkers are very useful to predict post-stroke recovery and individualized treatment.…”

Section: Discussionmentioning

confidence: 99%

Genetic plasma biomarkers associated with ischemic stroke

et al. 2023

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Aim: Stroke is one of the leading causes of death and disability worldwide. Plasma biomarkers have long been used to evaluate physiological or pathological processes and to make predictions about the outcome of stroke patients. The current systematic review is focused on genetic plasma biomarkers as a new potential prognostic indicator for post-stroke recovery. The aim of the present systematic review is to assess the potential of genetic plasma biomarkers associated with stroke to predict post-stroke recovery. Methods: The search strategy used PubMed and Web of Science databases to identified 166 studies that investigated genetic plasma biomarkers in patients with stroke between 2017 and 2021. However, only 21 of them met the inclusion criteria. Results: The identified genetic biomarkers can be divided into: (i) serum/plasma circular RNA (circRNA) associated with stroke onset or recurrence (5; 23.80%), (ii) genetic polymorphisms associated with the atherosclerotic process and stroke recurrence (6; 28.57%), (iii) serum/plasma long non-coding RNA (lncRNA) levels involved in immunity/inflammatory processes (4; 19.04%), (iv) marker of DNA methylation associated with stroke onset and outcome (3; 14.28%), and (v) proteins and pathways of stroke identified by serum/ plasma proteomics/genomics analysis (3; 14.28%). Conclusions: Overall, more than 100 potential biomarkers were found and the data suggest that combinations of plasma genetic biomarkers might be used as a better predictor for stroke.

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“…CircSHOC2 in ischemic preconditioning astrocyte exosome (IPAS-EXOs) effectively inhibits neuronal apoptosis and reduces neuronal damage with regulated autophagy on the miR-7670-3p/SIRT1 axis, which may develop IS treatment strategies [ 39 ]. A recent report discovered that hsaCirc0078299 and FXN might be considered as new biomarkers of IS to achieve neuroprotection and brain recovery from stroke [ 40 ].…”

Section: Role Of Circrna In Ismentioning

confidence: 99%