Mansouri Fatemeh, Seyed Mohammadzad Mirhosein
Department of Genetics and Immunology, Faculty of Medicine, Urmia University of Medical Sciences, Iran.
Cellular and Molecular Research Center, Urmia University of Medical Sciences, Iran.
Diab Vasc Dis Res. 2025 May-Jun;22(3):14791641251335925. doi: 10.1177/14791641251335925. Epub 2025 May 6.
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 ( < 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 ( < 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.
糖尿病患者患心血管疾病和心肌梗死（MI）的风险高出3至5倍。有必要寻找微小RNA（miRNA）和其他靶基因以降低死亡率。本研究旨在在心肌梗死患者、糖尿病前期心肌梗死患者（未使用二甲双胍者）和糖尿病心肌梗死患者（使用二甲双胍者）中寻找潜在的miRNA和靶基因。
通过微阵列分析鉴定候选miRNA，并通过实时聚合酶链反应（RT-PCR）评估其在对照组和患者组中的差异表达。从TargetScan、miRWalk和miRDB数据库中检索miR-1和miR-133a的潜在靶标。使用受试者工作特征（ROC）曲线分析评估miRNA的敏感性和特异性。
微阵列分析确定，与健康对照组相比，所有心肌梗死患者组中有16种miRNA的表达发生了显著变化。根据这些数据，选择了两种miR-1和miR-133a（比例较高）进行进一步验证。所有患者组中miR-1和miR-133a的表达水平均显著升高。此外，使用二甲双胍患者的miR-1和miR-133a水平低于未使用者（P<0.05）。此外，白细胞介素、生长因子和其他相关基因被确定为miR-1和miR-133a的潜在靶标。糖尿病患者循环miR-1的曲线下面积（AUC）为0.973（95%CI：0.718-0.884），miR-133a为0.969（95%CI：0.723-0.876）（P<0.001）。
预测miRNA谱和靶基因网络对无糖尿病和有糖尿病个体的心肌梗死早期诊断具有重要价值。二甲双胍治疗与心肌梗死相关miRNA的低表达有关，提示该药物具有心脏保护的潜在机制。
