Mol Cell Biochem. 2026 Jul 31. doi: 10.1007/s11010-026-05657-0. Online ahead of print.
ABSTRACT
Chronic heart failure (CHF) is a severe end-stage syndrome of multiple cardiovascular diseases, associated with unfavorable clinical prognosis. This study aimed to investigate the expression profile, clinical value and molecular mechanism of BCYRN1 in regulating myocardial cell injury in CHF. Quantitative real-time PCR (qRT-PCR) was applied to detect the expression level of BCYRN1. The Receiver operating characteristic (ROC) curves was used to evaluate its diagnostic performance, and Kaplan-Meier survival analysis was performed to explore the correlation between BCYRN1 and patient prognosis. Hydrogen peroxide (H₂O₂) was used to establish a cardiomyocyte injury model. CCK-8 assay, flow cytometry, ELISA, and Western blot were used to detect cell viability, the apoptosis rate, inflammatory cytokines secretion, and the proteins related to apoptosis, respectively. Dual-luciferase reporter assay was conducted to verify the molecular binding relationships. BCYRN1 and BAX were significantly upregulated, whereas miR-455-3p was downregulated in CHF patients. BCYRN1 exhibited reliable diagnostic efficacy for CHF; High BCYRN1 expression was correlated with lower 36-month survival. BCYRN1 knockdown improved cell viability, suppressed apoptosis and reduced inflammatory cytokine release in H₂O₂-treated cardiomyocytes. Mechanistic validation revealed that BCYRN1 acts as a competitive endogenous RNA (ceRNA) to sponge miR-455-3p, thereby releasing its inhibitory effect on BAX. Rescue experiments confirmed that inhibiting miR-455-3p abrogated the protective effect of BCYRN1 silencing on cardiomyocytes. Inhibiting BAX expression reversed the detrimental effects of the miR-455-3p inhibitor on cardiomyocytes. BCYRN1 may represent a potential biomarker for CHF diagnosis and prognosis. It worsens H2O2-driven inflammatory injury and apoptosis in cardiomyocytes via the miR-455-3p/BAX axis, which may represent a potential novel molecular target in CHF treatment.
PMID:42536139 | DOI:10.1007/s11010-026-05657-0