Identifying potential therapeutic targets for ischemic stroke through immune infiltration analysis and construction of a programmed cell death‑related ceRNA network

The present study aimed to uncover the underlying mechanisms and potential intervention targets of ischemic stroke (IS). An immune cell infiltration analysis using CIBERSORT was performed on two stroke-related datasets from the Gene Expression Omnibus database to generate a competitive endogenous RNA (ceRNA) network. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to predict potential biological functions of the network. Differentially expressed genes in the ceRNA network and programmed cell death-related genes were intersected to obtain common genes for a stroke ceRNA network related to programmed cell death. These genes were further verified through a middle cerebral artery occlusion rat model using reverse transcription-quantitative PCR. This built a ceRNA regulatory network based on bioinformatic analysis. In addition to the biological functions extracted from the GO and KEGG enrichment analyses, it was discovered that long non-coding (lnc)RNA-mediated ceRNA regulatory pathways were associated with programmed cell death. This included five for apoptosis (lncRNA deleted in lymphocytic leukemia 2 like (DLEU2L)/micro (miR)-4500/sulfite oxidase, lncRNA DLEU2L/miR-4500/transforming growth factor β receptor III, lncRNA DLEU2L/miR-4500/BTB and CNC homology 1 (BACH1), lncRNA DLEU2L/miR-4500/zinc finger and BTB domain containing 5 and lncRNA LINC00266-1/miR-363-3p/zinc finger protein 354B and two for ferroptosis (lncRNA DLEU2L/miR-4500/ribo-nucleotide reductase regulatory subunit M2 and lncRNA DLEU2L/miR-4500/BACH1). Based on the aforementioned results, the present study provided potential approaches for bridging programmed cell death, immune infiltration and ceRNA regulatory networks in IS. The present study may provide novel insights into the clinical diagnosis and treatment of IS, and may improve the knowledge of the regulation of pathophysiological processes for IS.