Key Words miR-24-3p • RIPK1 • Myocardial ischemia reperfusion injury Abstract Background/Aims: This study was developed to investigate a potential therapeutic method for myocardial ischemia/reperfusion injury involving the promotion of miR-24-3p expression. Methods: Microarray analysis was used to screen differentially expressed genes in a myocardial ischemia/reperfusion (I/R) injury mouse model. Gene set enrichment analysis was utilized to determine vital signaling pathways. Targeting

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... ion was conducted with a luciferase reporter assay. Myocardial I/R injury was developed in mice, and the expression levels of RIPK1 and miR-24-3p were investigated by qRT-PCR and Western blot. Hemodynamic parameters and the activity of serum myocardial enzymes were measured to evaluate cardiac function. Infarct area was observed through HE and TTC staining. Myocardial cell apoptosis was examined by TUNEL staining and caspase-3 activity analysis. Results: RIPK1 was an upregulated mRNA found by microarray analysis and a verified target of the downregulated miRNA miR-24-3p. The upregulation of RIPK1 (1.8-fold) and the downregulation of miR-24-3p (0.3-fold) were confirmed in I/R mice. RIPK1 led to impaired cardiac function indexes, increased infarct area and cell apoptosis, while miR-24-3p could reverse the injury by regulating RIPK1. The TNF signaling pathway was proven to be involved in myocardial I/R injury through the detection of the dysregulation of related proteins. Conclusion: In conclusion, RIPK1 was upregulated and miR-24-3p was downregulated in a myocardial I/R injury mouse model. RIPK1 could aggravate myocardial I/R injury via the TNF signaling pathway, while miR-24-3p could suppress RIPK1 and therefore exert cardioprotective effects in myocardial I/R injury. Tan et al.: Role of miR-24-3p in Myocardial Ischemia/Reperfusion Injury Fig. 1. Microarray analysis and KEGG and GO term enrichment analyses. (A) mRNA microarray analysis of ischemia/reperfusion (P<0.5, fold change>2); 16 of the most upregulated mRNAs are presented using a heatmap. (B) mRNA microarray analysis of ischemia/reperfusion (P<0.5, fold change>2); 10 of the most downregulated miRNAs are presented using a heatmap. (C) GSEA of GO (Gene Ontology) annotations. (D) KEGG analysis showed that the TNF pathway was highly expressed in the I/R mouse model.