MicroRNAs (miRNAs) are powerful regulators of protein expression. Many play important roles in cardiac development and disease. While several miRNAs and targets have been well characterized, the abundance of miRNAs and the numerous potential targets for each suggest that the vast majority of these interactions have yet to be described. The goal of this study was to characterize miRNA expression in the mouse heart after coronary artery ligation (LIG) and identify novel mRNA targets altered during the initial response to ischemic stress. We performed small RNA sequencing (RNA-Seq) of ischemic heart tissue 1 day and 3 days after ligation and identified 182 differentially expressed miRNAs. We then selected relevant mRNA targets from all potential targets by correlating miRNA and mRNA expression from a corresponding RNA-Seq data set. From this analysis we chose to focus, as proof of principle, on two miRNAs from the miR-125 family, miR-125a and miR-351, and two of their potential mRNA targets, Xin actin-binding repeat-containing protein 1 (XIRP1) and factor inhibiting hypoxia-inducible factor (FIH). We found miR-125a to be less abundant and XIRP1 more abundant after ligation. In contrast, the related murine miRNA miR-351 was substantially upregulated in response to ischemic injury, and FIH expression correspondingly decreased. Luciferase reporter assays confirmed direct interactions between these miRNAs and targets. In summary, we utilized a correlative analysis strategy combining miRNA and mRNA expression data to identify functional miRNA-mRNA relationships in the heart after ligation. These findings provide insight into the response to ischemic injury and suggest future therapeutic targets.

中文翻译：

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miR-125 家族调节 XIRP1 和 FIH 以响应心肌梗死。

MicroRNAs (miRNAs) 是蛋白质表达的强大调节剂。许多在心脏发育和疾病中起重要作用。虽然一些 miRNA 和靶标已经得到很好的表征，但 miRNA 的丰度和每种miRNA 的众多潜在靶标表明这些相互作用中的绝大多数尚未被描述。本研究的目的是表征冠状动脉结扎 (LIG) 后小鼠心脏中的 miRNA 表达，并确定在对缺血性应激的初始反应期间改变的新 mRNA 靶标。我们在结扎后 1 天和 3 天对缺血性心脏组织进行了小 RNA 测序 (RNA-Seq)，并鉴定了 182 个差异表达的 miRNA。然后，我们通过关联来自相应 RNA-Seq 数据集的 miRNA 和 mRNA 表达，从所有潜在目标中选择相关的 mRNA 目标。XIRP1）和抑制缺氧诱导因子（FIH）的因子。我们发现连接后 miR-125a 的丰度较低，而 XIRP1 的丰度更高。相比之下，相关的小鼠 miRNA miR-351 在缺血性损伤时显着上调，FIH 表达相应降低。荧光素酶报告基因检测证实了这些 miRNA 和靶标之间的直接相互作用。总之，我们利用结合 miRNA 和 mRNA 表达数据的相关分析策略来识别结扎后心脏中的功能性 miRNA-mRNA 关系。这些发现提供了对缺血性损伤反应的深入了解，并提出了未来的治疗目标。