The predictive value of miR-28-5p and miR-424-5p in metabolic syndrome and their mechanism of action through regulation of Fras-1-related extracellular matrix protein 2.

The prevalence of metabolic syndrome (MS) is rising due to lifestyle changes. To investigate the pathogenesis of MS and identify potential biomarkers, bioinformatics tools were used to screen for MS-related genes, such as Fras-1-related extracellular matrix protein 2 (FREM2), and miRNAs, including miR-28-5p and miR-424-5p. An insulin resistance (IR) cell model was established by treating human liver cells with insulin. The roles of FREM2, miR-28-5p, and miR-424-5p in IR were examined through overexpression and silencing experiments. Transfection of miR-28-5p/miR-424-5p mimics and a dual-luciferase assay were performed to explore their regulation of FREM2. The diagnostic value of miR-28-5p/miR-424-5p in MS was assessed using the receiver operating characteristic (ROC) curve. Increased expression of FREM2 and suppression of miR-28-5p/miR-424-5p enhanced glucose uptake in IR cells. Transfection with miR-28-5p or miR-424-5p mimics reduced luciferase activity in cells transfected with the wild-type FREM2 reporter vector and suppressed FREM2 expression. The ROC curve analysis indicated that miR-28-5p and miR-424-5p serve as effective classifiers for MS, with their combined use offering higher reliability. In conclusion, miR-28-5p and miR-424-5p exacerbated IR progression in human liver cells (HHL-5) through the negative regulation of FREM2, and they are potential biomarkers for MS.