Identification of Blood Circular RNAs as the Potential Biomarkers for Acute Ischemic Stroke
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE138849 | GEO | 2020/01/23
REPOSITORIES: GEO
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Project description:Stroke is one of the major causes of death and long-term disability, of which acute ischemic stroke (AIS) is the most common type. Although circRNA expression profiles of AIS patients have been reported to be significantly altered in blood and peripheral blood mononuclear cells, the role of exosome-contained circRNAs after AIS is still unknown. Plasma exosomes from ten AIS patients and ten controls were isolated, and through microarray and bioinformatics analysis, profile and putative function of circRNAs in the plasma exosomes were studied. A total of 198 circRNAs were differentially quantified (|log2 FoldChange|≥1.00, P<0.05) between AIS patients and controls.The functions of host genes of differentially quantified circRNAs, including RNA and protein process, focal adhesion and leukocyte transendothelial migration, were associated with the development of AIS. As miRNA sponge, differentially quantified circRNAs had the potential to regulate pathways related to AIS, like PI3K-Akt, AMPK and chemokine pathways. Of 198 differentially quantified circRNAs, 96 circRNAs possessing strong translational ability could affect cellular structure and activity, like focal adhesion, tight junction and endocytosis. Most differentially quantified circRNAs were predicted to bind to EIF4A3 and AGO2- two RNA binding proteins (RBPs)- and play a role in AIS. In conclusion, plasma exosome-derived circRNAs were significantly differentially quantified between AIS patients and controls, and participated in the occurrence and progression of AIS by sponging miRNA/RBPs or translating into proteins, indicating that circRNAs from plasma exosomes could be crucial molecules in the pathogenesis of AIS and promising candidates as diagnostic biomarkers and therapeutic targets for the condition.
2022-01-28 | GSE195442 | GEO
Project description:Background: Ischemic stroke is a disease with high rate of death and disability worldwide. This study investigated key circRNAs related to ischemic stroke. Methods: Three ischemic stroke patients and three healthy individuals were included in the current study to obtain the circRNA expression profiles by RNA sequencing. Through bioinformatic analysis, differentially expressed circRNAs (DEcircRNAs) were identified, and GO and pathway analyses for the host genes of DEcircRNAs were conducted. To further explore the functions of key circRNAs, a DEcircRNA-miRNA interaction network was constructed. Finally, the expression levels of selected circRNAs were validated with qRT-PCR. Results: A total of 736 DEcircRNAs were detected in ischemic stroke. Functional annotation of host genes of DEcircRNAs revealed several significantly enriched pathways, including Fc epsilon RI signaling pathway, B cell receptor signaling pathway, and T cell receptor signaling pathway. A circRNA-miRNA network, including 1544 circRNA-miRNA pairs, 456 circRNAs and 4 miRNAs, was obtained. The qRT-PCR results were largely in keeping with our RNA-seq data. Conclusion: The results of our study may help to elucidate the specific mechanism underlying ischemic stroke.
2021-06-24 | GSE178764 | GEO
Project description:Acute ischemic stroke (AIS) is a leading cause of disability and mortality worldwide. By high-throughput sequencing of infarct and ischemic penumbra tissue from middle cerebral artery embolization (MCAO) mice, we identified the CircRNA expression was dramatically and selectively regulated in the penumbra tissues.
2022-11-01 | GSE186103 | GEO
Project description:To investigate the potential involvement of circRNA in ischemic pathophysiology, we performed a circRNA microarray in an established transient middle cerebral artery occlusion (MCAO) mouse model of stroke. We evaluated the expression of 1797 circRNAs in adult mice brain after tMCAO. In our study, 5 of the 1178 circRNAs analyzed in the circRNA array were up-regulated significantly, ≥1.5-fold, in ischemic cortex at 12 hours of reperfusion after MCAO compared with their levels in sham group.
2020-09-25 | GSE115697 | GEO
Project description:Circular RNAs (circRNAs) are a recently discovered non-coding RNA isoform capable of regulating neurological disease incidence. The present study was designed to characterize the circRNA expression profiles present in large-artery atherosclerosis (LAA)-type acute ischemic stroke patients. Using a RNA-seq approach, we characterized circRNA expression profiles in 5 LAA-stroke patients and 4 controls. We identified 182 and 176 circRNAs that were up- and down-regulated, respectively, in LAA-stroke patients relative to controls. Enrichment analyses suggested these differentially expressed circRNAs to primarily be associated with chromatin modification, autophagy, platelet activation, and neural precursor cell proliferation.
2021-12-31 | GSE161913 | GEO
Project description:To explore circulating circRNAs associated with acute ischemia stroke(AIS), their utility as an early diagnostic marker and their significance in predicting stroke outcomes.
2020-11-04 | GSE133768 | GEO
Project description:Circular RNAs (circRNAs) are a large class of animal RNAs. To investigate possible circRNA functions, it is important to understand circRNA biogenesis. Besides human Alu repeats, sequence features that promote exon circularization are largely unknown. We experimentally identified new circRNAs in C. elegans. Reverse complementary sequences between introns bracketing circRNAs were significantly enriched compared to linear controls. By scoring the presence of reverse complementary sequences in human introns we predicted and experimentally validated novel circRNAs. We show that introns bracketing circRNAs are highly enriched in RNA editing or hyper-editing events. Knockdown of the double-strand RNA editing ADAR1 enzyme significantly and specifically up-regulated circRNA expression. Together, our data support a model of animal circRNA biogenesis in which competing RNA:RNA interactions of introns form larger structures which promote circularization of embedded exons, while ADAR1 antagonizes circRNA expression by melting stems within these interactions. Thus, we assign a new function to ADAR1. Examination of 12 samples in different stages of C.elegans development.
2015-01-06 | E-GEOD-63823 | biostudies-arrayexpress
Project description:Atrial fibrillation (AF) is the most common irregular heart rhythm which influence approximately 1–2% of the general population. As a potential factor for ischemic stroke, AF could also cause heart failure. The mechanisms behind AF pathogenesis are complex and remains elusive. As a new category of non-coding RNAs (ncRNAs), circular RNAs (circRNAs) have been known as the key of developmental processes, regulation of cell function, pathogenesis of heart diseases and pathological responses which could provide novel sight into the pathogenesis of AF. circRNAs function as modulators of microRNAs in cardiac disease. To investigate the regulatory mechanism of circRNA in atrial fibrillation, especially the complex interactions among circRNA, microRNA and mRNA, we collected the heart tissues from three AF patients and three healthy controls and profiled their circRNA expressions with circRNA Microarray. The differentially expressed circRNAs were identified and the biological functions of their interaction microRNAs and mRNAs were analyzed. Our results provided novel insights of the circRNA roles in atrial fibrillation and proposed highly possible interaction mechanisms among circRNAs, microRNAs and mRNAs.
2019-04-06 | GSE129409 | GEO
Project description:Circular RNAs (circRNAs) are an endogenous class of animal RNAs. Despite their abundance, their function and expression in the nervous system are unknown. Therefore, we sequenced RNA from different brain regions, primary neurons, isolated synapses, as well as during neuronal differentiation. Using these and other available data, we discovered and analyzed thousands of neuronal human and mouse circRNAs. circRNAs were extraordinarily enriched in the mammalian brain, well conserved in sequence, often expressed as circRNAs in both human and mouse, and sometimes even detected in Drosophila brains. circRNAs were overall upregulated during neuronal differentiation, highly enriched in synapses, and often differentially expressed compared to their mRNA isoforms. circRNA expression correlated negatively with expression of the RNA-editing enzyme ADAR1. Knockdown of ADAR1 induced elevated circRNA expression. Together, we provide a circRNA brain expression atlas and evidence for important circRNA functions and values as biomarkers. To assess circRNA expression in mammalian brain, we sequenced and analyzed mouse brain regions (hippocampus, cerebellum, prefrontal cortex and olfactory bulb), various neuronal differentiation (mouse P19 and human SH-SY5Y cells) and maturation (mouse cortical neurons) stages, and subcellular compartments in mouse (synaptoneurosomal fraction, cytoplasmic fraction, whole brain lysate).
2015-04-24 | E-GEOD-65926 | biostudies-arrayexpress
Project description:Background: Long noncoding RNAs (lncRNAs) have been confirmed to be associated with ischemic stroke (IS); however, their involvement still needs to be extensively explored. Therefore, we aimed to study the expression profile of lncRNAs and the potential roles and mechanisms of lncRNAs in the pathogenesis of acute ischemic stroke (AIS) in the Southern Chinese Han population. Methods: lncRNA and mRNA expression profiles in AIS were analyzed using high-throughput RNA sequencing (RNA-Seq) and validated using quantitative real-time polymerase chain reaction (qRT-PCR). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and network analyses were performed to predict the functions and interactions of the aberrantly expressed genes. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of lncRNAs in AIS. Results: RNA-Seq analysis showed that 428 lncRNAs and 957 mRNAs were significantly upregulated, while 791 lncRNAs and 4263 mRNAs were downregulated in patients with AIS when compared with healthy controls. GO enrichment and KEGG pathway analyses of differentially expressed genes showed that the apoptosis, inflammatory, oxidative and calcium signaling pathways were potentially implicated in AIS pathology. The PCR results showed that the selected lncRNA-C14orf64 and lncRNA-AC136007.2 were significantly downregulated in AIS. ROC curve analysis showed that the area under the ROC curve (AUC) values of lncRNA-C14orf64 and lncRNA-AC136007.2 between AIS and healthy controls were 0.74 and 0.94, respectively. Conclusion: This study provides evidence of altered expression of lncRNAs and their potential functions in AIS. Our findings may facilitate pathological mechanistic studies of lncRNAs in AIS and provide potential diagnostic biomarkers and therapeutic targets for AIS.
2019-11-13 | GSE140275 | GEO