MiR-6721-5p as a natural regulator of Meta-VCL is upregulated in the serum of patients with coronary artery disease.

BACKGROUND

Coronary artery disease (CAD), the leading cause of mortality globally, arises from atherosclerotic blockage of the coronary arteries. Meta-vinculin (meta-VCL), a large spliced isoform of VCL, co-localizes in muscular adhesive structures and plays significant roles in cardiac physiology and pathophysiology. This study aimed to identify microRNAs (miRNAs) regulating expression and investigate the expression alterations of the miRNAs of interest and as potential biomarkers in the serum of CAD patients.

METHODS

Bioinformatics tools were employed to select miRNAs targeting . Cell-based ectopic expression analysis and a dual-luciferase assay were used to examine the interactions between miRNAs and . An ELISA assessed the concentrations of interleukin-6 (IL-6), IL-10, and tumor necrosis factor-α (TNF-α). MiRNA and expression patterns and biomarker suitability were evaluated in serum samples from CAD and non-CAD individuals using real-time PCR. A cardiac cell-line data set and CAD blood exosome samples were analyzed using bioinformatics and ROC curve analyses, respectively.

RESULTS

miR-6721-5p directly interacted with the putative target sites at the 3'-UTR of meta-VCL and regulated its expression. IL-10 and TNF-α concentrations, which may act as anti-inflammatory factors, decreased following miR-6721-5p upregulation and downregulation. Bioinformatics and experimental expression analyses confirmed downregulated expression and upregulated miR-6721-5p expression in CAD samples. ROC curve analysis yielded an AUC score of 0.705 (P = 0.018), indicating the potential suitability of miR-6721-5p as a biomarker for CAD.

CONCLUSIONS

miR-6721-5p plays a regulatory role in expression and may contribute to CAD development by reducing anti-inflammatory factors. These findings suggest that miR-6721-5p could serve as a novel biomarker in the pathogenesis of CAD.