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Background: MicroRNAs (miRNAs) are part of the brain's response to ischemia. This study aimed to screen potential miRNAs for the prediction and novel treatments of ischemic stroke.Methods: Two mRNA and 1 miRNA microarray expression profile data were downloaded from the Gene Expression Omnibus database. Then, differentially expressed mRNAs and miRNAs were identified. Based on the miRNA-target pairs predicted, an miRNA-target interaction network was established. Bioinformatics analysis (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment) was applied to interpret the function of the miRNA targets.Results: In total, 16 differentially expressed miRNAs and 1345 differentially expressed genes were identified in ischemic stroke, respectively. Importantly, 445 miRNA-target pairs with an inverse correlation of expression were obtained, and the miRNA functional synergistic network was generated. Two miRNAs (miR-145 and miR-122) may represent potential biomarkers in ischemic stroke by being involved in the process of postischemic neuronal damage and thrombosis, respectively. Three novel miRNAs (miR-99b, miR-542-3p, and miR-455-5p) were deregulated, suggesting their roles in the pathological processes of ischemic stroke. Functional annotation indicated that apoptotic signaling cascades play an important role in patients with ischemic stroke.Conclusion: miR-145 and miR-122 represent new biomarkers and underlying targets for the prevention and treatment of ischemic stroke. [ABSTRACT FROM AUTHOR]

Our previous study indicated that microRNA 145 (miR-145) and its predicated target, erythropoietin-producing hepatoma (EPH) receptor A4 (EPHA4), was closely associated with ischemic stroke. In this study, we aimed to further explore their function in a model of oxygen-glucose deprivation (OGD). The expression of miR-145 in the blood of 44 patients with ischemic stroke and 37 normal controls was detected by qRT-PCR. After transfection with either the wild- or mutant-type pGL3-promoter EPHA4 3′UTR into the miR-145 mimic and miR-145 inhibitor, a dual-luciferase reporter assay was performed to explore the interaction between miR-145 and EPHA4. qRT-PCR and Western blot were performed to further explore the effects of miR-145 on EPHA4 expression after an miR-145 mimic, an miR-145 inhibitor or LV-sh-EPHA4 was transfected into cerebral cortical neurons. The expression of miR-145 was significantly upregulated in the blood of patients with ischemic stroke compared to that of normal controls. Dual-luciferase reporter assay, qRT-PCR and Western blot results indicated that miR-145 indeed targets EPHA4 through its 3′-UTR and regulates the expression level of EPHA4 at both the mRNA and protein levels. Moreover, the OGD model was successfully constructed, and miR-145 exerted a protective effects in cell viability in the OGD model by downregulating EPHA4. The expression of LOC105376244 could be regulated by the miR-145-EPHA4 interaction. MiR-145 exerted a protective effects in cell viability in the OGD model by downregulating EPHA4, which suggested their potential roles in ischemic stroke and requires further research. [ABSTRACT FROM AUTHOR]

Introduction: Ischemic stroke (IS) causes severe neurological impairments and physical disabilities and has a high economic burden. Our study aims to identify the key genes and upstream regulators in IS by integrated microarray analysis. Methods: An integrated analysis of microarray studies of IS was performed to identify the differentially expressed genes (DEGs) in IS compared to normal control. Based on these DEGs, we performed the functional annotation and transcriptional regulatory network constructions. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was performed to verify the expression of DEGs. Results: From two Gene Expression Omnibus datasets obtained, we obtained 1526 DEGs (534 up‐regulated and 992 down‐regulated genes) between IS and normal control. The results of functional annotation showed that Oxidative phosphorylation and Alzheimer's disease were significantly enriched pathways in IS. Top four transcription factors (TFs) with the most downstream genes including PAX4, POU2F1, ELK1, and NKX2‐5. The expression of six genes (ID3, ICAM2, DCTPP1, ANTXR2, DUSP1, and RGS2) was detected by qRT‐PCR. Except for DUSP1 and RGS2, the other four genes in qRT‐PCR played the same pattern with that in our integrated analysis. Conclusions: The dysregulation of these six genes may involve with the process of ischemic stroke (IS). Four TFs (PAX4, POU2F1, ELK1 and NKX2‐5) were concluded to play a role in IS. Our finding provided clues for exploring mechanism and developing novel diagnostic and therapeutic strategies for IS. [ABSTRACT FROM AUTHOR]

A previous study described the important regulatory roles of microRNAs (miRNAs) in ischemic stroke. However, the functional significance of long non-coding RNA (lncRNAs) in ischemic stroke was largely unknown. This study aimed to identify lncRNA profiling and elucidate the regulatory mechanisms in the pathophysiology of stroke. RNA sequencing was performed on the blood of three ischemic stroke patients and three normal controls. Differential expression analysis was used to identify differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs). After further correlation and co-expression analysis, the corresponding co-expression networks and miRN–lncRNA–mRNA interaction network were then constructed. The expression of DElncRNAs and DEmRNAs was verified in Gene Expression Omnibus. RNA sequencing and subsequent bioinformatics analysis produced a total of 61 DElncRNAs (14 upregulated and 47 downregulated) and 673 DEmRNAs (432 upregulated and 241 downregulated). LOC105372881 and LOC101929707 were the most highly increased and decreased lncRNAs in ischemic stroke. LncRNA–mRNA co-expression networks were constructed according to 3,008 positively co-expressed and 607 negatively co-expressed lncRNA–mRNA pairs. The DElncRNAs may play roles in the pathways of glycolysis/gluconeogenesis, arrhythmogenic right ventricular cardiomyopathy, adherens junction, lysosome, and hematopoietic cell lineage by regulating their co-expressed mRNAs. Combined with previous data, a miRNA–lncRNA–mRNA interaction network for ischemic stroke was constructed. Based on GSE22255, the expression of six DElncRNAs (CEBPA-AS1, LINC00884, HCG27, MATN1-AS1, HCG26, and LINC01184) and 11 DEmRNAs (TREML4, AHSP, PI3, TESC, ANXA3, OAS1, OAS2, IFI6, ISG15, IFI44L, and LY6E) was similar to the current sequencing data. This study is the first to identify blood lncRNAs in human ischemic stroke using RNA sequencing. The findings may be the foundation for understanding the potential role of lncRNAs in ischemic stroke. [ABSTRACT FROM AUTHOR]