Abstract
Background: Acute ischemic stroke (AIS) is the second leading cause of death and the third leading cause of disability worldwide. Long noncoding RNAs (lncRNAs) are promising biomarkers for the early diagnosis of AIS and closely participate in the mechanism of stroke onset. However, studies focusing on lncRNAs functioning as microRNA (miRNA) sponges to regulate the mRNA expression are rare and superficial. Methods: In this study, we systematically analyzed the expression profiles of lncRNA, mRNA (GSE58294), and miRNA (GSE110993) from the GEO database. Gene ontology (GO) analysis was performed to reveal the functions of differentially expressed genes (DEGs), and we used weighted gene co-expression network analysis (WGCNA) to investigate the relationships between clinical features and expression profiles and the co-expression of miRNA and lncRNA. Finally, we constructed a lncRNA–miRNA–mRNA competing endogenous RNA (ceRNA) network with selected DEGs using bioinformatics methods and obtained ROC curves to assess the diagnostic efficacy of differentially expressed lncRNAs (DElncRNAs) and differentially expressed mRNAs (DEmRNAs) in our network. The GSE22255 dataset was used to confirm the diagnostic value of candidate genes. Results: In total, 199 DElncRNAs, 2068 DEmRNAs, and 96 differentially expressed miRNAs were detected. The GO analysis revealed that DEmRNAs primarily participate in neutrophil activation, neutrophil degranulation, vacuolar transport, and lysosomal transport. WGCNA screened out 16 lncRNAs and 195 mRNAs from DEGs, and only eight DElncRNAs maintained an area under the curve higher than 0.9. By investigating the relationships between lncRNAs and mRNAs, a ceRNA network containing three lncRNAs, three miRNAs, and seven mRNAs was constructed. GSE22255 confirmed that RP1-193H18.2 is more advantageous for diagnosing stroke, whereas no mRNA showed realistic diagnostic efficacy. Conclusion: The ceRNA network may broaden our understanding of AIS pathology, and the candidate lncRNA from the ceRNA network is assumed to be a promising therapeutic target and diagnostic biomarker for AIS.
Highlights
Stroke is the second leading cause of death and the third leading cause of disability in adults (Campbell and Khatri, 2020)
2068 Differentially expressed mRNAs (DEmRNAs) and 199 DElncRNAs were identified between stroke patients and healthy controls from GSE58294, including 1564 upregulated and 504 downregulated mRNAs, as well as 104 upregulated and 95 downregulated Long noncoding RNAs (lncRNAs)
It showed that DEmRNAs and DElncRNAs spread to all autosomes and the X chromosome, and none of them were found in the Y chromosome
Summary
Stroke is the second leading cause of death and the third leading cause of disability in adults (Campbell and Khatri, 2020). Safe and successful rehabilitation for stroke is strictly limited by the therapeutic time window (Emberson et al, 2014), which renders early diagnosis extremely critical. The diagnosis of ischemic stroke primarily depends on typical clinical symptoms and auxiliary brain imaging examinations (Campbell and Khatri, 2020). Acute ischemic stroke (AIS) is the second leading cause of death and the third leading cause of disability worldwide. Long noncoding RNAs (lncRNAs) are promising biomarkers for the early diagnosis of AIS and closely participate in the mechanism of stroke onset. Studies focusing on lncRNAs functioning as microRNA (miRNA) sponges to regulate the mRNA expression are rare and superficial
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