A p53-responsive microRNA-100 released from cardiomyoblasts serves as an early biomarker for acute coronary syndrome

Coronary artery disease, a leading cause of mortality, underscores the need for biomarkers that can predict acute coronary syndrome (ACS) occurrence and outcomes. MicroRNAs (miRNAs) are increasingly recognized as potential markers. This study aimed to identify a plasma miRNA signature in ACS patients undergoing elective cardiac catheterization and to investigate miR-100's potential as an ACS prognostic biomarker. Plasma samples from 100 patients with suspected ACS were analyzed. qPCR revealed significantly elevated plasma miR-29a-3p, miR-100, miR-192, and miR-194-5p in ACS patients, and multiplex ELISA showed increased myeloperoxidase. Sub-network enrichment analysis identified TP53 as a central regulator of the miRNA-gene interaction network. In H9c2 cardiomyoblasts, hypoxic treatment (1% O₂) induced significant cytotoxicity and increased intracellular and released miR-100 levels. Western blotting further showed that hypoxia suppressed p53, HMGB1, NF-κB, and Bcl-2 expression. Consistent with the predicted regulatory network, siRNA-mediated p53 silencing markedly reduced constitutive miR-100 expression and triggered compensatory upregulation of inflammatory and survival-related proteins, including TLR4, NF-κB, and Bcl-2. Conversely, miR-100 overexpression significantly increased p53 protein levels and reduced the pro-survival factor Mcl-1, whereas miR-100 inhibition produced the opposite effect. These findings define a reciprocal p53/miR-100 regulatory axis that influences inflammatory and survival signaling in cardiomyoblasts. In conclusion, both clinical profiling and mechanistic studies support miR-100 as a promising early prognostic biomarker for ACS and suggest that hypoxia-induced disruption of the p53/miR-100 axis may contribute to cardiomyoblast vulnerability. Further studies are warranted to explore its therapeutic potential.