PDF(Pubmed)
Abstract：
Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) is a carboxypeptidase B-like proenzyme encoded by the CPB2 gene. After thrombin activation, TAFI downregulates fibrinolysis, thus linking the latter with coagulation. TAFI has been shown to play a role in venous and arterial thrombotic diseases, yet, data regarding the molecular mechanisms underlying its function have been conflicting. In this study, we focused on the prediction and functional enrichment analysis (FEA) of the TAFI interaction network and the microRNAs (miRNAs) targeting the members of this network in an attempt to identify novel components and pathways of TAFI-related thrombosis. To this end, we used nine bioinformatics software tools. We found that the TAFI interactome consists of 28 unique genes mainly involved in hemostasis. Twenty-four miRNAs were predicted to target these genes. Co-annotation analysis of the predicted interactors with respect to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and transcription factors (TFs) pointed to the complement and coagulation cascades as well as neutrophil extracellular trap formation. Cancer, stroke, and intracranial aneurysm were among the top 20 significant diseases related to the identified miRNAs. We reason that the predicted biomolecules should be further studied in the context of TAFI-related thrombosis.
摘要：
凝血酶激活的纤溶抑制剂(TAFI)是由CPB2基因编码的羧肽酶B样酶原。凝血酶活化后,TAFI下调纤维蛋白溶解,从而将后者与凝血联系起来。TAFI已被证明在静脉和动脉血栓性疾病中起作用，然而，关于其功能背后的分子机制的数据一直相互矛盾。在这项研究中,我们重点研究了TAFI相互作用网络的预测和功能富集分析(FEA)以及靶向该网络成员的microRNAs(miRNAs),试图鉴定TAFI相关血栓形成的新成分和通路.为此,我们使用了九个生物信息学软件工具。我们发现TAFI相互作用组由28个主要参与止血的独特基因组成。预测24个miRNA靶向这些基因。关于京都基因和基因组百科全书（KEGG）途径和转录因子（TF）的预测相互作用物的共注释分析指出了补体和凝血级联反应以及中性粒细胞胞外陷阱的形成。癌症,中风,和颅内动脉瘤是与鉴定的miRNAs相关的前20种重要疾病之一。我们认为预测的生物分子应该在TAFI相关血栓形成的背景下进一步研究。
