Identification of microRNAs enriched in exosomes in human pericardial fluid of patients with atrial fibrillation based on bioinformatic analysis.
Identification of microRNAs enriched in exosomes in human pericardial fluid of patients with atrial fibrillation based on bioinformatic analysis.
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基于生物信息学分析的心房颤动患者心包液中外泌体富集的microRNA鉴定
DOI：
10.21037/jtd-20-2066
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发表时间：
2020-10
影响因子：
2.5
通讯作者：
Luo F
中科院分区：
文献类型：
--
作者：
Liu L;Chen Y;Shu J;Tang CE;Jiang Y;Luo F
研究背景心房颤动（AF）与心房结构和电重构有关。心房纤维化的发展和进展是结构重构的特征，并被视为AF永久化的基质。越来越多的证据证实microRNAs（miRNAs）与AF（包括心脏纤维化）相关。方法收集9例先天性心脏病合并持续性房颤或窦性心律（SR）的成年患者的心包液（PF）。获得异常表达的miRNAs，以P2<0.05 and fold change >作为差异表达miRNAs（DE-miRNAs）的阈值。通过miRTarBase软件获得预测的目的基因。注释、可视化和集成发现数据库用于注释功能并分析DE-miRNA的潜在靶标的途径丰度。利用STRING数据库构建蛋白质-蛋白质相互作用（PPI）网络，并利用Cytoscape软件可视化miRNA-hub基因-京都基因与基因组百科全书（KEGG）网络。通过定量聚合酶链反应（qPCR）评估DE-miRNA表达。结果在AF和SR样本中发现了55个外泌体DE-miRNA;其中包括24个上调的miRNA和31个下调的miRNA。对于前3种下调的miRNA（miR-382- 3 p、miR-3126- 5 p和miR-450 a-2- 3 p），确定了283个预测的靶基因，这些基因与心脏纤维化相关通路有关，包括缺氧诱导因子-1（HIF 1）、丝裂原活化蛋白激酶（MAPK）以及肾上腺素能和胰岛素通路。PPI网络中的前10个枢纽基因，包括促分裂原活化蛋白激酶1（MAPK 1）和AKT丝氨酸/苏氨酸激酶1（AKT 1），被确定为枢纽基因。通过构建miRNA-hub基因-KEGG网络，我们观察到这些受miR-382- 3 p、miR-3126- 5 p和miR-450 a-2- 3 p调控的hub基因参与了许多与心脏纤维化相关的KEGG通路，如AKT 1/糖原合成酶激酶-3 β（GSK-3β）和转化生长因子-β（TGF-β）/MAPK 1通路。结论人PF exosomes中的miR-382- 3 p、miR-450 a-2- 3 p和miR-3126- 5 p在AF的发生发展中起着关键作用。qPCR结果显示miR-382- 3 p与我们的测序结果一致，提示其作为AF治疗靶点的潜在价值。
Background Atrial fibrillation (AF) is related to structural and electrical atria remodeling. Atrial fibrosis development and progression is characteristic of structural remodeling and is taken as the AF perpetuation substrate. Increasing evidence has confirmed that microRNAs (miRNAs) are associated with AF, including cardiac fibrosis. Methods Pericardial fluid (PF) samples were collected from nine adult patients who had congenital heart disease with persistent AF or sinus rhythm (SR) undergoing surgery. Abnormally expressed miRNAs were acquired, and P<0.05 and fold change >2 were taken as the thresholds of differentially expressed miRNAs (DE-miRNAs). The predicted target genes were obtained by miRTarBase. The Database for Annotation, Visualization and Integrated Discovery was used to annotate functions and analyze pathway abundance for latent targets of DE-miRNAs. STRING database was applied to construct a protein–protein interplay (PPI) network, and Cytoscape software was used to visualize the miRNA-hub gene-Kyoto Encyclopedia of Genes and Genomes (KEGG) network. DE-miRNA expressions were evaluated by quantitative polymerase chain reaction (qPCR). Results Fifty-five exosomal DE-miRNAs were found between the AF and SR samples; these included 24 miRNAs that were upregulated and 31 that were downregulated. For the top 3 downregulated miRNAs (miR-382-3p, miR-3126-5p, and miR-450a-2-3p) 283 predicted target genes were identified, and were implicated in cardiac fibrosis-related pathways, including the hypoxia-inducible factor-1 (HIF1), mitogen-activated protein kinase (MAPK), and adrenergic and insulin pathways. The top 10 hub genes in the PPI network, including mitogen-activated protein kinase 1 (MAPK1) and AKT serine/threonine kinase 1 (AKT1), were identified as hub genes. By establishing the miRNA-hub gene-KEGG network, we observed that these hub genes, which were regulated by miR-382-3p, miR-3126-5p, and miR-450a-2-3p, were involved in many KEGG pathways associated with cardiac fibrosis, such as the AKT1/glycogen synthase kinsase-3β (GSK-3β) and transforming growth factor-β (TGF-β)/MAPK1 pathways. Conclusions The findings of the present study suggest that miR-382-3p, miR-450a-2-3p, and miR-3126-5p contained in exosomes in human PF are pivotal in the progression of AF. The results of qPCR showed that miR-382-3p was consistent with our sequencing data, which indicates its potential value as a therapeutic target for AF.
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6.7
作者：
Shephard, P;Hinz, B;Smola, H
通讯作者：
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影响因子：
44.1
作者：
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通讯作者：
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