Bioinformatics analyses of potential microRNAs and their target genes in myocardial infarction patients with diabetes.

Abstract

ObjectivePatients with diabetes are 3-5 times higher at risk for cardiovascular diseases and myocardial infarction (MI). There is a need to find miRNAs and other target genes to reduce mortality rates. The current study aims to find potential miRNAs and target genes among MI patients, MI patients with pre-diabetes (metformin non-users), and MI patients with diabetes (metformin users).MethodThe candidate miRNAs were identified by microarray profiling, and their differential expression was evaluated through real-time polymerase chain reaction (RT-PCR) in control and patient groups. The potential targets for miR-1 and miR-133a were retrieved from the TargetScan, miRWalk, and miRDB databases. The sensitivity and specificity of miRNAs were assessed using receiver operating characteristic (ROC) curve analyses.ResultsMicroarray profiling identified 16 miRNAs with significantly altered expression in all MI patient groups compared with healthy controls. According to this data, two miR-1 and miR-133a (with a high ratio) were selected for further verification. All patient groups exhibited a significant increase in the expression levels of miR-1 and miR-133a. Also, miR-1 and miR-133a levels were lower in metformin-user patients than in non-user patients (p < 0.05). Moreover, interleukins, growth factors, and other related genes were identified as potential targets for miR-1 and miR-133a. The ROC area under the curve (AUC) was 0.973 (95% CI: 0.718-0.884) for circulating miR-1, and 0.969 (95% CI: 0.723-0.876) for miR-133a in patients with diabetes (p < 0.001).ConclusionPrediction of miRNA profiles and network of target genes are valuable in the early diagnosis of MI in individuals without and with diabetes. Metformin treatment is associated with lower expression of MI-related miRNAs, suggesting a potential mechanism for cardiac protection by this agent.