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基于 CTD、GeneCards 和 PharmGKB 数据库的急性创伤性凝血功能障碍相关 lncRNA-miRNA-mRNA 共表达调控网络的筛选。

Screening of lncRNA-miRNA-mRNA Coexpression Regulatory Networks Involved in Acute Traumatic Coagulation Dysfunction Based on CTD, GeneCards, and PharmGKB Databases.

机构信息

Hengyang Medical School, University of South China, Hengyang 421001, China.

Critical Care Medicine & Trauma Centre, The Second Affiliated Hospital of the University of South China, Hengyang 421000, China.

出版信息

Oxid Med Cell Longev. 2022 Apr 19;2022:7280312. doi: 10.1155/2022/7280312. eCollection 2022.

Abstract

Competitive endogenous RNA (ceRNA) networks play crucial roles in multiple biological processes and development of diseases. They might serve as diagnostic and prognosis markers as well as therapeutic targets. The purpose of this study was to identify a novel ceRNA network involving KCNQ1OT1, hsa-miR-24-3p, and VWF in acute traumatic coagulopathy (ATC) based on databases search. We searched the CTD, GeneCards, and PharmGKB databases for ATC-related target genes using Coagulopathy as a keyword. Upstream miRNAs and lncRNAs of the candidate target VWF were then explored using the miRWalk, microT, TargetScan, RNA22 and Tarbase, and DIANA-LncBase and Starbase databases, respectively. A KCNQ1OT1-hsa-miR-24-3p-VWF ceRNA network was constructed by "ggalluvial" package. Interaction between KCNQ1OT1, hsa-miR-24-3p, and VWF was examined, and their expression was quantified in the peripheral blood samples from 30 ATC patients and liver tissues of ATC rat models. Forty-one ATC-related target genes were identified following data retrieval from publicly available databases, of which VWF was selected as the target and used for the subsequent analysis. KCNQ1OT1 and hsa-miR-24-3p were confirmed to be the key upstream regulatory factors of VWF. KCNQ1OT1-hsa-miR-24-3p-VWF coexpression regulatory network was constructed where KCNQ1OT1 competitively bound to hsa-miR-24-3p and attenuated its binding to VWF. Both the liver tissues of ATC rats and peripheral blood samples from ATC patients showed increased hsa-miR-24-3p expression and decreased VWF and KCNQ1OT1 expression. Collectively, we described the KCNQ1OT1-hsa-miR-24-3p-VWF ceRNA network in the development of ATC. We propose a new ceRNA that could help in the diagnosis and treatment of ATC.

摘要

竞争性内源性 RNA (ceRNA) 网络在多种生物过程和疾病的发生发展中发挥着关键作用。它们可能作为诊断和预后标志物以及治疗靶点。本研究旨在通过数据库检索,确定一个涉及 KCNQ1OT1、hsa-miR-24-3p 和 VWF 的急性创伤性凝血病 (ATC) 的新型 ceRNA 网络。我们使用“Coagulopathy”作为关键词,在 CTD、GeneCards 和 PharmGKB 数据库中搜索与 ATC 相关的靶基因。然后,分别使用 miRWalk、microT、TargetScan、RNA22 和 Tarbase、DIANA-LncBase 和 Starbase 数据库来探索候选靶标 VWF 的上游 miRNA 和 lncRNA。通过“ggalluvial”包构建 KCNQ1OT1-hsa-miR-24-3p-VWF ceRNA 网络。通过荧光素酶报告基因实验检测 KCNQ1OT1、hsa-miR-24-3p 和 VWF 之间的相互作用,并在 30 例 ATC 患者的外周血样本和 ATC 大鼠模型的肝组织中定量检测其表达。从公开数据库中检索数据后,确定了 41 个与 ATC 相关的靶基因,其中选择 VWF 作为靶标进行后续分析。证实 KCNQ1OT1 和 hsa-miR-24-3p 是 VWF 的关键上游调控因子。构建了 KCNQ1OT1-hsa-miR-24-3p-VWF 共表达调控网络,其中 KCNQ1OT1 竞争性结合 hsa-miR-24-3p,减弱其与 VWF 的结合。ATC 大鼠肝组织和 ATC 患者外周血样本均显示 hsa-miR-24-3p 表达增加,VWF 和 KCNQ1OT1 表达降低。总之,我们描述了 ATC 发展过程中的 KCNQ1OT1-hsa-miR-24-3p-VWF ceRNA 网络。我们提出了一个新的 ceRNA,可能有助于 ATC 的诊断和治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f8/9042625/30f2954d7e88/OMCL2022-7280312.001.jpg

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