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.
Accumulating evidence has noted the circRNA-microRNA- (circRNA-miRNA-) mRNA competing endogenous RNA (ceRNA) regulatory network in disease development and progression. The current study explored the ceRNA network in acute traumatic coagulopathy (ATC). Potential ATC-related genes were screened, and upstream miRNAs and circRNAs of VWF (the candidate target) were assayed through database searching and high-throughput sequencing technology. circ_0001274/miR-143-3p/VWF ceRNA regulatory network was constructed and validated. The expression of circ_0001274/miR-143-3p/VWF was determined in the peripheral blood samples from ATC patients and ATC mouse models. Online database and circRNA sequencing analysis results identified VWF as a key gene in ATC as supported by assays and that VWF was lowly expressed in ATC patients and mice. Further experiments demonstrated that miR-143-3p could target and inhibit VWF, and circ_0001274 could competitively sponge miR-143-3p. Functionally, circ_0001274 could competitively sequester miR-143-3p to upregulate VWF expression, potentially improving ATC. Our study highlights the critical role of circ_0001274/miR-143-3p/VWF axis in improving ATC.
BACKGROUND: Mounting evidence has shown that long noncoding RNAs (lncRNAs) can function as competing endogenous RNAs (ceRNAs) which participate in the initiation and progression of cancers. In the ceRNA network, lncRNAs, microRNAs (miRNAs) and mRNAs, communicate with and co-regulate each other. Rarely there is a systematic lncRNA-mediated ceRNA network and potential specific ceRNA pairs or triples of esophageal cancer (EC). In this study, we investigate the lncRNA-mediated ceRNA network in EC and screen the potential prognostic lncRNA biomarkers.METHODS: We obtained mRNA, miRNA, and lncRNA expression data and relevant clinical features on patients with EC from The Cancer Genome Atlas (TCGA), and used the edgR package to identify differentially expressed mRNAs, lncRNAs and miRNAs between EC samples and normal samples. The EC ceRNA network was constructed based on miRNA target prediction through the databases of miRcode, miRDB, miRTarBase and TargetScan. And then Pearson’s correlation analysis was adopted to identify co-expression mRNA-lncRNA pairs. Finally, the robust likelihood-based survival analysis and Cox regression models were used to identify prognosis-related lncRNAs, which was evaluated by Kaplan-Meier and receiver operating characteristic (ROC) curve analysis.RESULTS: A total of 3,200 mRNAs, 131 miRNAs and 1,338 lncRNAs were identified as significantly differentially expressed in EC, of which, 30 mRNAs, 15 lncRNAs, and 8 miRNAs were incorporated in the ceRNA network. According to the ceRNA network node degrees, lncRNA MAGI2-AS3, hsa-mir-93 and TGFBR2 were the key genes. Also, the ceRNA network revealed some important ceRNA pairs and triples, such as SNX29P2-TGFBR2 and MAGI2-AS-hsa-mir-143-COL1A1. Finally, we developed a six-lncRNA signature (ZNF341-AS1, AC130324.2, AC027271.1, AL591212.1, AL732314.4 and LOC105372352), with improved diagnostic potential for EC with the area under the ROC curve of 0.93.CONCLUSIONS: our present work sheds new light on the tumorigenesis roles of lncRNA-mediated ceRNA network in EC and identifies a six‐lncRNA model that could be used as candidate prognostic signature.
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