Background: Venous thromboembolism (VTE) is a major global health problem with high incidence and mortality. Vein endothelial cell (VEC) dysfunction is the primary cause of VTE. MicroRNAs (miRNAs) assist in the regulation of VEC functional pathways. Our objective was to identify potential miRNA target genes associated with VTE.
Materials and methods: To explore the association between mRNAs and miRNAs in VTE, we performed an mRNA or miRNA microarray analysis and experiments in vitro. In addition, five online bioinformatics tools identified the target genes of differentially expressed miRNAs, and a miRNA-gene network was constructed. As a result, hub miRNA and mRNA were confirmed. Finally, wound healing assay and transwell migration assay were performed to elucidate the effect of hub miRNA in VEC. Luciferase reporter assay and real-time quantitative polymerase chain reaction (RT-qPCR) were performed to decide the role of miRNA in the expression of hub mRNA.
Results: Screening identified eight overlapping dysregulated genes in patients with VTE, three of which demonstrated a significantly decreased expression of miR-200a-5p. Low expression miR-200a-5p in VTE patients is confirmed by a receiver operating characteristic analysis (AUC = 0.800, P = 0.023) and binary logistic regression (OR = 0.359, 95% confidence interval: 0.605-0.995). RT-qPCR results showed that the miR-200a-5p level was decreased in hypoxia VEC (P = 0.038). MiR-200a-5p significantly promoted the migration ability of VEC. The result of Dual-luciferase reporter assay showed that cytochrome coxidase Ⅶc (COX7C) directly inhibit the miR-200a-5p expression by binding 5'UTR of miR-200a-5p (P = 0.011).
Conclusions: We anticipate that the miR-200a-5p-COX7C pair might be involved in the progression of VTE. Moreover, miR-200a-5p might be a therapeutic target for VTE.
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.