Abstract
BackgroundClopidogrel resistance (CR) increases the risk of atherothrombotic events. Emerging evidence suggests that circRNAs may influence pharmacodynamic responses to clopidogrel. MethodsA total of 25 CR and 25 non-clopidogrel resistance (NCR) patients were enrolled. To identify circRNAs and miRNAs associated with CR, a microarray analysis was performed on RNA samples from 5 CR and 5 NCR patients. Based on the 10 most dysregulated circRNAs, a circRNA-miRNA network was constructed to explore target interactions. Next, the expression of selected circRNAs and their targeted mRNAs was measured, and their diagnostic value for CR was evaluated. Through joint analysis, the candidate miRNAs were identified and verified by RT‒PCR. Finally, after THLE-2 cells were cultivated and transfected with plasmids, the interactions among circ_007695, miR-4512 and COL19A1 were detected. ResultsOur present study revealed circRNA and miRNA microarray expression profiles in CR and NCR patients and constructed a circRNA‒miRNA network. Moreover, in the CR group, hsa_circ_0076837, hsa_circ_0057714, and hsa_circ_0076957 were downregulated, and the mRNA expression of AOX1 and COL19A1 was also lower in these CR patients. ROC curve analysis indicated that hsa_circ_0057714 (targeting AOX1) and hsa_circ_0076957 (targeting COL19A1) may serve as reliable biomarkers for distinguishing CR. Furthermore, we revealed that the level of miR-4512 was greater in CR and circ-0076957 could regulate COL19A1 expression by targeting miR4512 in THLE-2 cells. ConclusionThese findings highlight hsa_circ_0057714 and hsa_circ_0076957 as novel biomarkers for CR and suggest that circ-0076957 may regulate COL19A1 expression by targeting miR-4512, providing insights that could improve management of clopidogrel resistance in CAD.
Published Version
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