circRNA-Associated ceRNA Regulatory Networks in Cardiac Responses to High-Altitude Hypoxia in Tibetan Pigs (Sus scrofa).

High-altitude hypoxic adaptation in mammals involves complex molecular mechanisms, with non-coding RNAs (ncRNAs) increasingly reported to participate in hypoxia-related regulation. However, the contribution of circRNAs in cardiac adaptation to chronic hypoxia remains largely unexplored. This study performed an integrative competitive endogenous RNA (ceRNA) analysis to investigate circRNA-mediated regulatory networks in the hearts of Tibetan pigs and Yorkshire pigs maintained under high- and low-altitude conditions, using four comparison groups (TH, TL, YH, and YL). Using Ribo-Zero RNA sequencing, we identified 961 circRNAs in heart tissues, with 358 differentially expressed circRNAs (DE-circRNAs) detected across the four groups. Functional enrichment analysis revealed that their host genes were associated with hypoxia-related pathways, including HIF-1, VEGF, AMPK, and autophagy, critical for energy metabolism and mitochondrial function. A HIF-1-specific ceRNA network was constructed, identifying key axes including circDUSP16-ssc-miR-671-5p-CAMK2A, circTLK1-ssc-miR-331-3p-SERPINE1, and circTLK1-novel-miR-624-ENO1. JASPAR analysis predicted potential HIF-1α binding sites in the promoters of ENO1, SERPINE1, and CAMK2A, supporting their regulatory roles. These findings provide a transcriptomic overview of circRNA expression patterns in pig heart tissues under different altitude conditions and prioritize candidate ceRNA relationships for further functional investigation.