Screening and Analysis of Potential Critical Gene in Acute Myocardial Infarction Based on a miRNA-mRNA Regulatory Network

Abstract

Background MicroRNAs (miRNAs) have been shown to be involved in the initiation, progression, and prevention of acute myocardial infarction (AMI), but the underlying mechanism remains unclear. Objective Through the GEO database, bioinformatics methods were used to explore the miRNA-mRNA regulatory relationship pairs associated with AMI and to elucidate the underlying mechanism. Methods Using the R software Limma package, differential expression analysis was performed using the AMI-related miRNA chip dataset (GSE31568) and mRNA chip dataset (GSE159657) from the GEO database. The miRDB, miRWalk, miRTarBase, and TargetScan databases were used to predict potential downstream target genes regulated by differentially expressed miRNAs, and a miRNA-mRNA regulatory network was built with Cytoscape; GO function and KEGG pathway enrichment analyses of target genes were done with Funrich software, and the protein interaction network of target genes in the regulatory network was built with the STRING database. Results and Conclusions A total of 187 differentially expressed miRNAs were experimentally screened, of which 91 were upregulated (such as hsa-miR-302b, hsa-miR-1299), and 96 were downregulated (such as hsa-miR-1201, hsa-miR-1283); 507 differentially expressed mRNAs were identified, of which 430 were upregulated (such as MRM1 and SFXN4), and 77 were downregulated (such as KCTD13 and CCDC134). And 16 miRNAs and 44 mRNAs were used for regulatory network construction. GO and KEGG enrichment analyses mainly focused on Integrins in angiogenesis, angiopoietin receptor Tie2-mediated signaling, and signaling events mediated by stem cell factor receptor (c-Kit). As hub genes in the PPI network, FGF2 and MMP2 may be key targets of AMI. The experimentally constructed miRNA-mRNA regulatory network found that hsa-miR-190b targets to inhibit FGF2, while hsa-miR-330-3p targets to regulate MMP2, which may mediate Integrins in angiogenesis, Angiopoietin receptor Tie2-mediated signaling pathway to induce AMI pathogenesis, providing strong data support and a research direction for the prevention and treatment of AMI.

Comprehensive Analysis of Sideroflexin 4 in Hepatocellular Carcinoma by Bioinformatics and Experiments

“…SFXN4 knockout in zebrafish caused mitochondrial respiratory defect and resulted in macrocytic anemia 23 . Furthermore, mutation in SFXN4 is correlated with prenatal onset of mitochondrial diseases, and presented with macrocytic anemia and optic nerve hypoplasia 43 , 44 . Recent studies revealed that SFXN1 and SFXN4 regulate mitochondrial respiratory chain through different mechanisms, SFXN1 was reported to the maintain the integrity of mitochondrial complex Ⅲ 14 , while SFXN4 coordinates the assembly of complex Ⅰ by interacting with MCIA complex, integrating mtDNA-encoded ND6 and promoting ND2-module maturation 45 .…”

“…By GWAS meta-analysis, SFXN4 SNP (rs150807690) was found to be implicated in stroke, suggesting SFXN4 was a potential ischemic stroke loci11 48 . Based on bioinformatics analysis, it was found that SFXN4 expression was upregulated during acute myocardial infarction 44 . Recently, Dang et al found that SFXN4 was upregulated in lung adenocarcinoma, and it had significant correlation with immune infiltration 49 .…”