Objective:To analyze and verify the expression of ISL1 gene in myocardial infarction, and explore its mechanism of action in myocardial infarction.Methods:By analyzing the chip expression profile data in the GEO database, the expression characteristics of the ISL1 gene in myocardial infarction, as well as the highly co expressed related genes and enriched pathway functions of the ISL1 gene, were identified. Patients with myocardial infarction and their healthy controls were included, and the expression of genes such as ISL1 and GRIN2D was verified using real-time polymerase chain reaction (RT-PCR).Results:The expression level of ISL1 gene in myocardial infarction samples was higher than that in the control group samples. In the GSE59867 and GSE29111 datasets, there are a total of 152, 231, and 329 intersections of the top 2000, top 2500, and top 3000 related genes, respectively. The functional annotation of co-expressed genes revealed that intersection genes were closely related to organ development, matrix protein formation, epithelial cell differentiation, and the activity of related signaling pathways during embryonic development. Finally, in the construction of the ISL1 related ceRNA regulatory network, 12 genes were located in the ISL1 top 2000 related mating set, and together with miRNAs, they participated in the formation of 21 pairs of miRNA-mRNA. And through multiple queues, the key regulatory gene was identified as GRIN2D, which competitively bound to multiple miRNAs with ISL1 and its expression was highly negatively correlated with ISL1 in two independent datassets ( r=-0.52, -0.41). The RT-PCR results showed that the expression levels of miR-128-3p, miR 27a-3p, and miR-27b-3p in the acute myocardial infarction group were lower than those in the control group, while the expression levels of ISL1 and GRIN2D were higher than those in the control group (all P<0.01). Conclusions:ISL1 may play a protective role in myocardial infarction by participating in the formation of matrix proteins, differentiation of epithelial cells, and activity of related signaling pathways.