Rouka Erasmia, Zarogiannis Sotirios G, Hatzoglou Chrissi, Gourgoulianis Konstantinos I, Malli Foteini
Department of Nursing, School of Health Sciences, University of Thessaly, GAIOPOLIS, 41500 Larissa, Greece.
Department of Physiology, Faculty of Medicine, School of Health Sciences, University of Thessaly, BIOPOLIS, 41500 Larissa, Greece.
Biomolecules. 2023 Aug 28;13(9):1318. doi: 10.3390/biom13091318.
Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) is a carboxypeptidase B-like proenzyme encoded by the 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.
凝血酶激活的纤维蛋白溶解抑制剂(TAFI)是一种由该基因编码的羧肽酶B样前体酶。凝血酶激活后,TAFI下调纤维蛋白溶解,从而将其与凝血联系起来。TAFI已被证明在静脉和动脉血栓性疾病中起作用,然而,关于其功能潜在分子机制的数据一直存在矛盾。在本研究中,我们专注于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微小RNA(miRNA),试图识别TAFI相关血栓形成的新成分和途径。为此,我们使用了九种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。预测有24种miRNA靶向这些基因。对预测的相互作用分子进行京都基因与基因组百科全书(KEGG)途径和转录因子(TF)的共注释分析,指向补体和凝血级联以及中性粒细胞胞外陷阱形成。癌症、中风和颅内动脉瘤是与已鉴定的miRNA相关的前20种重大疾病。我们认为,预测的生物分子应在TAFI相关血栓形成的背景下进一步研究。