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静脉血栓栓塞症患者循环 miRNA 和外周全血基因表达谱的相关性和整合。

Correlation and integration of circulating miRNA and peripheral whole blood gene expression profiles in patients with venous thromboembolism.

机构信息

Emergency and Acute Critical Care Department, Huashan Hospital North, Fudan University, Shanghai, China.

出版信息

Bioengineered. 2021 Dec;12(1):2352-2363. doi: 10.1080/21655979.2021.1935401.

Abstract

The main aim of this work was to evaluate differential expression and biological functions of circulating miRNA and whole peripheral blood (PB) genes in patients affected by venous thromboembolism (VTE) and in healthy subjects. Circulating miRNA sequences and PB expression profiles were obtained from GEO datasets. Ten miRNAs with the most significant differential expression rate (dif-miRNA) were subjected to miRbase to confirm their identity. Dif-miRNA targets were predicted by TargetScan and aligned with differentially expressed genes to obtain overlapping co-genes. Biological functions of co-genes were analyzed by Gene Ontology and KEGG analysis. Interaction network of dif-miRNAs, co-genes, and their downstream pathways were studied by analyzing protein-protein interaction (PPI) clusters (STRING) and determining the crucial hubs (Cytoscape).MiR-522-3p and miR-134 dif-miRNAs are involved in protein translation and apoptosis by regulating their respective co-genes in PB. Co-genes are present in nucleolus and extracellular exosomes and are involved in oxidative phosphorylation and ribosome/poly(A)-RNA organization. The predicted PPI network covered 107 clustered genes and 220 marginal joints, where ten hub genes participating in PPIs were found. All these hub genes were down-regulated in VTE patients. Our study identifies new miRNAs as potential biological markers and therapeutic targets for VTE.

摘要

本研究旨在评估静脉血栓栓塞症 (VTE) 患者和健康对照者外周血循环 miRNA 和全血基因的差异表达和生物学功能。从 GEO 数据集获得循环 miRNA 序列和 PB 表达谱。对差异表达最显著的 10 个 miRNA(差异 miRNA,dif-miRNA)进行 miRBase 验证以确认其身份。使用 TargetScan 预测 dif-miRNA 靶标,并与差异表达基因对齐以获得重叠的共同基因。通过 Gene Ontology 和 KEGG 分析对共同基因的生物学功能进行分析。通过分析蛋白质-蛋白质相互作用 (PPI) 簇(STRING)和确定关键枢纽(Cytoscape)来研究 dif-miRNA、共同基因及其下游途径的互作网络。miR-522-3p 和 miR-134 dif-miRNAs 通过调节 PB 中的各自共同基因参与蛋白质翻译和细胞凋亡。共同基因存在于核仁中和细胞外的外泌体中,参与氧化磷酸化和核糖体/多聚(A)-RNA 组织。预测的 PPI 网络涵盖 107 个聚类基因和 220 个边缘关节,其中发现了 10 个参与 PPI 的枢纽基因。所有这些枢纽基因在 VTE 患者中均下调。我们的研究确定了新的 miRNA 作为 VTE 的潜在生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b84/8806583/d2f8c07fd26a/KBIE_A_1935401_UF0001_OC.jpg

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