Exploratory analysis of relevant circRNA-mediated ceRNA networks in left ventricular cardiac tissue and liquid biopsy of heart failure individuals

Heart failure (HF) is a complex cardiovascular syndrome characterized by extensive molecular remodeling involving coding and non-coding RNAs. Among these, circular RNAs (circRNAs) have been proposed as potential regulators of gene expression, through competing endogenous RNA (ceRNA)-like mechanisms. In this study, we performed an integrative transcriptomic analysis using publicly available cardiac tissue RNA-seq datasets to identify differentially expressed circRNAs, miRNAs, and mRNAs associated with HF. Predicted RNA-RNA interactions were used to assemble putative circRNA-mediated ceRNA networks, followed by functional enrichment analyses to highlight biologically relevant pathways and molecular axes. In parallel, selected network components were evaluated by RT-qPCR in an independent, non-phenotype-matched plasma cohort, as an exploratory assessment of circulating expression patterns. Differential expression analyses identified multiple dysregulated RNAs associated with inflammatory signaling, cardiac remodeling, and calcium-related pathways. Integrative network analysis suggested the circMYH7_0072/hsa-let-7i-5p/ KCNN4 axis as a putative regulatory interaction potentially associated with HF-related molecular remodeling. Among the evaluated candidates, circMYH7_0072 was the only transcript that retained statistical significance after sex-, age- and pharmacological-adjusted regression and FDR correction in the exploratory plasma cohort. Given the demographic and clinical imbalance of this cohort, this finding should be interpreted as a hypothesis-generating result. Collectively, these findings are consistent with the potential involvement of circRNA-mediated regulatory networks in HF, although additional validation will be necessary to confirm their biological and translational relevance.