miR-15a-5p as a potential biomarker for hypertrophic cardiomyopathy and its bioinformatics analysis

Abstract Objectives Hypertrophic cardiomyopathy (HCM) is a common clinical Cardiac abnormality manifested as myocardial hypertrophy and diastolic dysfunction. This study investigated the role and clinical relevance of miR-15a-5p in HCM. Methods 220 participants were enrolled, including 110 HCM patients and 110 healthy controls. The abundance of miR-15a-5p and IRS1 were quantified by qRT-PCR. Pearson correlation and ROC curve was used to evaluate clinical relevance and diagnostic potential. The interaction between miR-15a-5p and IRS1 was confirmed through a dual-luciferase reporter assay. An isoproterenol (ISO)-induced hypertrophic model was established in H9c2 cardiomyocytes. The impacts of miR-15a-5p/IRS1 axis on hypertrophy-related genes (ANP, BNP, β-MHC) were quantified. Results miR-15a-5p was significantly elevated in HCM patients and positively correlated with disease severity, particularly maximum wall thickness. miR-15a-5p exhibited strong diagnostic potential and was shown to promote cardiomyocyte hypertrophy by directly targeting and downregulating IRS1. Functional experiments confirmed that suppression of miR-15a-5p alleviated ISO-induced level of hypertrophy markers, while IRS1 silencing reversed these effects. Enrichment analysis further suggested that miR-15a-5p is potentially implicated in key hypertrophy-related signaling pathways, including the AMPK pathway. Conclusions This study demonstrates that miR-15a-5p contributes to HCM progression by negatively regulating IRS1 and promoting cardiomyocyte hypertrophy. miR-15a-5p holds promise as a diagnostic candidate for myocardial hypertrophy in HCM.