Integrative multi-omics analysis reveals the drug-protein-ceRNA regulatory network in acute ischemic stroke

Previous studies have shown that non coding RNA (ncRNA) is closely related to the occurrence and development of acute ischemic stroke (AIS), but its systemic regulatory disease profile has not been fully elucidated. We collected peripheral whole blood samples from AIS patients and healthy controls for transcriptome expression profiling analysis of mRNA, micro RNA, and long non coding RNA (lncRNA). In transcriptome data analysis, differentially expressed RNAs were identified, and key functional pathways and microenvironmental changes in AIS were comprehensively analyzed. Based on the ceRNA hypothesis, a competitive regulatory network of ceRNA (lncRNA/miRNA/mRNA) for AIS disease occurrence was constructed. In downstream analysis, the upregulated mRNA in the ceRNA network was combined with drug target molecular information in the Drugbank database to screen and identify three direct targets, NFKBIA, TNFAIP6, and ORM1, all of which play key immunomodulatory and anti-inflammatory roles in the pathological process of AIS; Further combining with the PPI network, FN1 and MMP9 were identified as key predictive targets. Constructing a multi-level and multi-omics network map of drug protein ceRNA to explore the transformation pathway from molecular mechanisms to clinical drug targets. Molecular docking simulation was used to verify that the predicted targets FN1 and MMP9 can bind to current therapeutic drugs such as Acetylsalicylic acid, suggesting the possibility of FN1 and MMP9 as new targets for AIS treatment. This study follows a systematic strategy from constructing transcriptome regulatory networks to downstream clinical drug target validation, providing a new perspective for the occurrence and development of AIS diseases from the RNA regulatory level. The multi-omics landscape reveals potential molecular mechanisms and lays a solid theoretical foundation for identifying novel and reliable diagnostic biomarkers and potential therapeutic targets.