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

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 $R$ “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.