Vamp8 modulates cerebral ischemia-reperfusion injury via the autophagy-lysosome pathway

Lysosomal autophagy plays a critical role in ensuring the continuity of autophagic flux, however bioinformatics studies investigating biomarkers associated with lysosomal autophagy in cerebral ischemia-reperfusion injury(CIRI) remain scarce. Three datasets (GSE61616, GSE97537, and GSE82146) were retrieved from the GEO database. After batch correction, GSE61616 and GSE97537 were integrated into a combined dataset, while GSE82146 served as the validation set. Lysosomal autophagy-related genes (LRGs) obtained from the GeneCards database were intersected with differentially expressed genes (DEGs) identified between the CIRI group and the control group, resulting in the identification of 36 lysosomal autophagy-related differentially expressed genes (LRDEGs). Functional enrichment analysis using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) revealed that LRDEGs are primarily involved in biological processes such as membrane fusion and SNARE binding and are significantly enriched in inflammation-related pathways. We built a diagnostic model for CIRI and identified the biomarkers Vamp8. The results were further validated by quantitative real-time PCR (qPCR) and Western blotting. Simultaneously, immune infiltration analysis was performed. Finally, the mRNA-miRNA and mRNA-RBP interaction regulatory networks of the key genes revealed that Vamp8 is regulated by miR-325-3p, Elavl1, Zfp36, and Pabpc1.