Department of Biofunctional Informatics, Tokyo Medical and Dental University (TMDU).
Department of Bio-informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University (TMDU).
Circ J. 2018 Mar 23;82(4):965-973. doi: 10.1253/circj.CJ-17-1194. Epub 2018 Feb 5.
Recent experimental studies have demonstrated that several microRNAs (miRNAs) expressed in atrial tissue promote a substrate of atrial fibrillation (AF). However, because it has not been fully elucidated whether these experimental data contribute to identifying circulating miRNAs as biomarkers for AF, we used a combined analysis of human serum and murine atrial samples with the aim of identifying these biomarkers for predicting AF.
Comprehensive analyses were performed to screen 733 miRNAs in serum from 10 AF patients and 5 controls, and 672 miRNAs in atrial tissue from 6 inducible atrial tachycardia model mice and 3 controls. We selected miRNAs for which expression was detected in both analyses, and their expression levels were changed in the human analyses, the murine analyses, or both. This screening identified 11 candidate miRNAs. Next, we quantified the selected miRNAs using a quantitative RT-PCR in 50 AF and 50 non-AF subjects. The individual assessment revealed that 4 miRNAs (miR-99a-5p, miR-192-5p, miR-214-3p, and miR-342-5p) were significantly upregulated in AF patients. A receiver-operating characteristics curve indicated that miR-214-3p and miR-342-5p had the highest accuracy. The combination of the 4 miRNAs modestly improved the predictive accuracy for AF (76% sensitivity, 80% specificity).
Novel circulating miRNAs were upregulated in the serum of AF patients and might be potential biomarkers of AF.
最近的实验研究表明，在心房组织中表达的几种 microRNAs（miRNAs）促进了房颤（AF）的底物。然而，由于尚未充分阐明这些实验数据是否有助于将循环 miRNAs 鉴定为 AF 的生物标志物，我们使用了对人血清和鼠心房样本的综合分析，旨在鉴定这些预测 AF 的生物标志物。
对来自 10 名 AF 患者和 5 名对照者的血清中的 733 个 miRNAs 进行了全面分析，并对来自 6 只可诱导性心房性心动过速模型鼠和 3 名对照者的心房组织中的 672 个 miRNAs 进行了分析。我们选择了在这两种分析中均有表达的 miRNAs，其表达水平在人分析、鼠分析或两者中均发生了改变。该筛选确定了 11 个候选 miRNAs。接下来，我们使用定量 RT-PCR 在 50 名 AF 患者和 50 名非 AF 患者中对选定的 miRNAs 进行了定量。个体评估显示，在 AF 患者中，有 4 个 miRNAs（miR-99a-5p、miR-192-5p、miR-214-3p 和 miR-342-5p）表达显著上调。ROC 曲线表明，miR-214-3p 和 miR-342-5p 具有最高的准确性。这 4 个 miRNAs 的组合略微提高了对 AF 的预测准确性（76%的敏感性，80%的特异性）。
新型循环 miRNAs 在 AF 患者的血清中上调，可能是 AF 的潜在生物标志物。
