Identification of an miRNA Regulatory Network and Candidate Markers for Ischemic Stroke Related to Diabetes

PURPOSE: Type 2 diabetes mellitus (T2DM) increases the risk of ischemic stroke and poor prognosis. This study aimed to identify molecular mechanisms that are dysregulated in T2DM-associated ischemic stroke and candidate genes that might serve as biomarkers. METHODS: The top 25% variance genes in the GSE21321 and GSE22255 datasets were analyzed for coexpression. The differentially expressed mRNAs (DEmRs) between patients with T2DM or ischemic stroke and controls were analyzed. Then, the union of overlapping coexpressed genes and overlapping DEmRs was analyzed. The miRNAs differentially expressed in T2DM-associated ischemic stroke were also analyzed. CIBERSORT was used to evaluate the levels of infiltration by immune cells in T2DM-associated stroke. RESULTS: Thirteen coexpression modules were identified in T2DM and 10 in ischemic stroke, and 594 module genes were shared between the two conditions. A total of 4452 mRNAs differentially expressed between T2DM patients and controls were identified, as were 2390 mRNAs differentially expressed between ischemic stroke and controls. The 771 union genes were enriched mainly in immune-related biological functions and signaling pathways. UBE2N, TGFB3, EXOSC1, and VIM were identified as candidate markers. In addition, we identified miR-576-3p as having the most regulatory roles in both T2DM and ischemic stroke. Mast cell activation was significantly down-regulated in T2DM but up-regulated in ischemic stroke. CONCLUSION: These findings provide numerous testable hypotheses about the pathways underlying T2DM-associated ischemic stroke, which may help identify therapeutic targets.