Exploring the shared biomarkers between acute ischemia stroke and diabetes by transcriptome sequencing

Abstract

Objective: This study aimed to identify shared genetic signatures and potential molecular mechanisms linking acute ischemic stroke (AIS) and diabetes by analyzing their transcriptomic profiles. We sought to characterize differentially expressed non-coding RNAs (ncRNAs) and mRNAs, elucidate their functional pathways, and construct regulatory networks to uncover cross-talk between these conditions.

Methodology: Peripheral blood samples were collected from 5 AIS patients and 5 diabetic patients at the First Affiliated Hospital of Dali University between March 1 to September 31, 2023. Transcriptome sequencing was performed on blood samples from patients with comorbid AIS and diabetes, alongside healthy controls. Differentially expressed miRNAs (n=1,755), mRNAs (n=24,862), lncRNAs (n=7,387), and circRNAs (n=16,413) were identified (fold change >2, FDR <0.05). Functional enrichment was analyzed via GO and KEGG pathways. A ceRNA network integrating miRNA-mRNA-lncRNA-circRNA interactions was reconstructed using Cytoscape, with key regulators validated by degree centrality analysis.

Results: Top dysregulated transcripts included hsa-miR-3614-5p (up) and hsa-miR-935 (down), mRNAs ENSG00000100985/ENSG00000154764, lncRNAs ENSG00000268734/ENSG00000272529, and circRNAs hsa-circ-0027541/hsa-circ-0024837. Pathway analysis revealed: (1) circRNAs modulated T-cell receptor signaling and NK cell cytotoxicity. (2)miRNA-target genes enriched in cancer/stem cell pathways (e.g., PI3K-Akt). (3) mRNAs implicated in inflammatory cascades (TNF/NF-κB). (4)The ceRNA network demonstrated 756 interactions centered on hsa-miR-619-5p, which coordinated mRNA-lncRNA-circRNA cross-talk.

Conclusion: We identified convergent transcriptomic alterations in AIS-diabetes comorbidity, highlighting hsa-miR-619-5p as a hub regulator of immune-metabolic crosstalk. The integrated ceRNA network provides a mechanistic framework linking ncRNAs to inflammatory pathways, offering potential diagnostic biomarkers and therapeutic targets for dual disease management.