基于生物信息学方法分析心肌梗死大鼠miRNA芯片

Identification and function analysis of differentially expressed miRNAs in rat myocardial infarction model

目的筛选大鼠梗死心肌组织microarray芯片中差异表达的miRNA,预测其互作lncRNA和靶基因,探索心肌梗死潜在的病理机制。方法结扎左前降支冠状动脉建立大鼠心梗模型。应用TRIzol法提取梗死左心室心肌区总RNA进行芯片检测。用生物信息学方法找出可能存在的lncRNA-miRNA-mRNA调控网络。结果19个明显差异表达的miRNAs中8个miRNAs(miR-21、miR-132、miR-222、miR-223-3p、miR-146a/b、miR-181b、miR-449a-5p、miR-122)已被证明是治疗心梗的候选分子,7个miRNAs(miR-365-5p、miR-490-5p、miR-6333、miR-30c-1-3p、miR-3591、miR-3596c、miR-877)是否与心肌梗死有关未知。心肌梗死发生发展中可能存在几条新的lncRNA-miRNA-mRNA作用机制。ENSRNOT00000076620-miR-146b-5p-STAT3/Rnf7/Qrsl1可能参与梗死心肌细胞的凋亡和线粒体损伤过程。ENSRNOT00000071991-miR-122-Deptor可能抑制心肌细胞自噬的发生,加剧心肌梗死的过程。NR_132625-miR-21-3P/miR-18a-5p-Coq5/Acsl1/Tmem65可能参与心肌梗死线粒体损伤过程。结论通过心肌梗死大鼠miRNA芯片分析得到的lncRNA-miRNA-mRNA三元关系,为深入研究心肌梗死分子水平的病理机制,揭示相关药物作用机制以及寻找治疗新靶标提供方向和理论依据。

Aim To identify differentially expressed microRNAs(miRNAs)in rat myocardial infarcted tissues and predict their interaction with lncRNAs and target genes,as well as to explore potential pathophysiology mechanisms in myocardial infarction.Methods A rat model of myocardial infarction was established by ligating the left anterior descending coronary artery.Trizolwas used to extract total RNA from infarcted myocardial area for microarray detection.Bioinformatics methods were used to predict interaction lncRNAs,target genes,and functional enrichment of miRNAs thatwere significantly differently expressed.The possible lncRNA-miRNA-mRNA regulatory networks were identified finally.Results The elevation of ST segment of ECG showed that the rat model of myocardial infarction was successfully prepared.Microarray results showed that there were 19 significantly differently expressed miRNAs.Eight of these miRNAs(miR-21,miR-132,miR-222,miR-223-3p,miR-146a/b,miR-181b,miR-449a-5p,miR-122)were proven to be myocardial infarction treatment candidates.Whether seven miRNAs(miR-365-5p,miR-490-5p,miR-6333,miR-30c-1-3p,miR-3591,miR-3596c,miR-877)were related to myocardial infarction called for further confirmation.There might be several new lncRNA-miRNA-mRNA mechanisms in the development of myocardial infarction.ENSRNOT00000076620-miR-146b-5p-STAT3/Rnf7/Qrsl1 may be involved in the process of cardiomyocyte apoptosis and mitochondrial damage during myocardial infarction.ENSRNOT00000071991-miR-122-Deptor might inhibit the autophagy of cardiomyocytes and exacerbate myocardial infarction.Conclusions The ternary relationship of lncRNA-miRNA-mRNA obtained in this study may provide possible research directions and a certain theoretical basis for further exploration of the molecular level pathological mechanism of myocardial infarction,and new therapeutic targets for myocardial infarction as well.