Differentially expressed miRNAs in circulating exosomes between atrial fibrillation and sinus rhythm
Differentially expressed miRNAs in circulating exosomes between atrial fibrillation and sinus rhythm
复制标题
房颤和窦性心律循环外泌体中差异表达的 miRNA
DOI：
10.21037/jtd.2019.09.50
复制
发表时间：
2019-10-01
影响因子：
2.5
通讯作者：
Wang, Zhinong
中科院分区：
文献类型：
--
作者：
Wang, Suyu;Min, Jie;Wang, Zhinong
背景：外泌体是由细胞释放的小（30-150 nm）膜囊泡，其传递细胞间信息。microRNAs（miRNAs）作为exosomes的内容物之一，可能在心房颤动（AF）的发病机制中发挥重要作用。外泌体miRNAs作为生物标志物在AF中发挥潜在的作用，正如在许多其他疾病中所显示的那样。方法：为了鉴定持续性AF和窦性心律（SR）患者之间血浆外泌体miRNAs的不同表达水平，我们对AF（n=4）和SR（n=4）患者的外泌体中的小RNA进行了高通量测序。预测DE miRNAs的靶基因，并进行基因本体分析和通路分析。在验证阶段，我们对AF（n=40）和SR（n=20）患者中的6种DE miRNA进行了定量实时逆转录聚合酶链反应（qRT-PCR）。采用单因素和多因素Logistic回归分析房颤的危险因素。结果：通过高通量测序，我们在循环外泌体中发现了39个差异表达（DE）miRNA。我们使用qRT-PCR验证了4种DE血浆外泌体miRNA（miR-483- 5 p、miR-142- 5 p、miR-223- 3 p、miR-223- 5 p）。单因素Logistic回归分析显示miR-483- 5 p、miR-142- 5 p、miR-223- 3 p与AF相关，多因素Logistic回归分析显示miR-483- 5 p与AF独立相关。这一发现为研究房颤复杂的发病机制开辟了新的视角，而DE血浆外泌体miRNAs在评估房颤的严重程度或预后方面发挥着巨大的生物标志物作用并帮助选择治疗策略。
Background: Exosomes are small (30-150 nm) membrane vesicles released by cells that transmit intercellular information. As one of the contents of exosomes, microRNAs (miRNAs) may play an important role in the pathogenesis of atrial fibrillation (AF). Exosomal miRNAs potentially function as biomarkers in AF, as shown in many other diseases.Methods: To identify the different expression level of plasma exosomal miRNAs between persistent AF and sinus rhythm (SR) patients, we performed high-throughput sequencing of small RNAs in the exosomes of AF (n=4) and SR (n=4) patients. Target genes of the DE miRNAs were predicted and put into gene ontology analysis and pathway analysis. In the validation phase, we performed quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) of 6 of the DE miRNAs in AF (n=40) and SR (n=20) patients. Univariate and multivariate logistic analysis were used to analyze risk factors of AF.Results: With high-throughput sequencing, we revealed 39 differentially expressed (DE) miRNAs in circulating exosomes. We validated 4 of the DE plasma exosomal miRNAs (miR-483-5p, miR-142-5p, miR-223-3p, miR-223-5p) using qRT-PCR. Univariate logistic analysis shows miR-483-5p, miR-142-5p, miR-223-3p are related with AF, while multivariate logistic analysis suggests miR-483-5p is independently in correlation with AF.Conclusions: This discovery opens up a new perspective in the complicated mechanism underlying AF and the DE plasma exosomal miRNAs exert enormous potential of acting as biomarkers in assessing severity or prognostic of AF and help selecting therapeutic strategy.