NGS-identified circulating miR-375 as a potential regulating component of myocardial infarction associated network
NGS-identified circulating miR-375 as a potential regulating component of myocardial infarction associated network
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DOI：
10.1016/j.yjmcc.2018.07.129
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发表时间：
2018-08-01
影响因子：
5
通讯作者：
Favorova, Olga
中科院分区：
文献类型：
--
作者：
Baulina, Natalia;Osmak, German;Favorova, Olga
急性心肌梗死（MI）是最严重的冠心病类型，是全世界残疾和死亡的主要原因。为了研究 miRNA 在与 MI 相关的病理过程中的参与，我们使用下一代测序对 MI 患者外周血浆中的循环 miRNA（稳定的短非编码 RNA 分子）与健康对照（所有人均为男性，居住在俄罗斯欧洲地区）进行了分析。我们观察到 20 种 miRNA，其血浆水平在 MI 患者中相差两倍以上 (p < 0.05)。其中 miR-208b 和 miR-375 通过了多重校正阈值（分别为 FC = 49.2，FDR 调整后的 p 值 = 0.0078 和 FC = -6.4，FDR 调整后的 p 值 = 0.00076）；然后使用 RT-qPCR 验证这些数据（分别为 FC = 5.3，p 值 = 0.028 和 FC = -2.1，p 值 = 0.0039）。对于 miR-208b，我们重新鉴定了之前的观察结果，而 miR-375 首次被发现与 MI 相关。为了研究 miR-375 在 MI 中的循环 miRNA 中占有特殊地位的原因，对 miR-375 靶基因及其相互作用进行了富集和网络分析。 PIK3CA 和 TP53 基因受 miR-375 调节，被确定为 MI 疾病模块的关键参与者。
Acute myocardial infarction (MI), the most severe type of coronary heart disease, is a leading cause of disability and mortality worldwide. In order to investigate the involvement of miRNAs in the pathologic processes related to MI, we performed the analysis of circulating miRNAs - stable short noncoding RNA molecules - in the peripheral blood plasma of MI patients compared to healthy controls (all persons were men and lived in European Russia) using next generation sequencing. We observed 20 miRNAs, which levels in plasma more than two-fold differed in MI patients (p < 0.05). Among them miR-208b and miR-375 passed threshold for multiple corrections (FC = 49.2, FDR-adjusted p-value = 0.0078 and FC = -6.4, FDR-adjusted p-value = 0.00076, respectively); these data were then validated using RT-qPCR (FC = 5.3, p-value = 0.028 and FC = -2.1, p-value = 0.0039, respectively). While for miR-208b we reidentified earlier observations, miR-375 was found to be associated with MI for the first time. To investigate the reasons for which miR-375 holds a special place among circulating miRNAs in MI, enrichment and network analyses of miR-375 target genes and their interactions were carried out. PIK3CA and TP53 genes, regulated by miR-375, were identified as the key players of MI disease module.