Abstract
As a leading cause of death globally, stroke is a severe neurological disorder, with ischemic stroke (IS) being its most prevalent form. Given the time-sensitive nature of effective treatment, there is an urgent need for novel diagnostic and therapeutic targets. Noncoding long RNAs (lncRNAs), which regulate pathological processes, hold promise as a research area. However, their role in acute IS patients warrants further investigation. This study is designed to examine the molecular foundations of differentially expressed lncRNAs in acute IS and to assess their viability as biomarkers and therapeutic targets. We conducted an pilot study on acute IS involving a case group of 3 patients and a control group of 3 nonstroke individuals with matched clinical characteristics. High-throughput lncRNA sequencing of peripheral blood mononuclear cells was performed using the Illumina NovaSeq platform to identify differentially expressed lncRNAs. Bioinformatics analyses, including gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein-protein interaction (PPI) network, and pathway crossover analyses, were applied to explore the role of lncRNAs in stroke pathogenesis. A total of 1280 differentially expressed lncRNAs were identified, including 100 characterized and 1180 uncharacterized ones. GO analysis showed that these lncRNAs were mainly enriched in cellular membrane dynamics, regulation of enzymatic and kinase activities, and immune-inflammatory responses. KEGG pathway analysis indicated their primary association with the PI3K-Akt, cAMP, MAPK, and Rap1 signaling pathways. Further analysis suggested that LINC01820 may affect stroke pathology by modulating key genes such as AKT1, MAPK1, and VEGFA in the PI3K-Akt and MAPK pathways. LINC01820 exhibits significant differential expression in acute IS patients in this pilot study and may affect stroke pathology via the PI3K-Akt/MAPK pathway. Validation in larger, diverse cohorts is needed to establish its potential as a diagnostic biomarker or therapeutic target.