Breed-by-Altitude Interaction Reveals Cardiac miRNA–mRNA Regulatory Hubs Associated with Hypoxia Adaptation in Tibetan Pigs
- 1Frontiers Science Center for Molecular Design Breeding, China Agricultural University, Beijing 100193, China
- 2National Engineering Laboratory for Animal Breeding, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
- 3Department of Animal Husbandry, Xizang Agricultural and Animal Husbandry University, Linzhi 860000, China
Abstract
MicroRNAs (miRNAs) are important post-transcriptional regulators of cardiac responses to hypoxia, but how breed and altitude interact to shape cardiac miRNA expression remains unclear. We used a 2 × 2 factorial design involving Tibetan and Yorkshire pigs raised at high (3000 m) or low (100 m) altitude. Small RNA sequencing identified 1104 miRNAs, including 370 known and 734 putative novel miRNA candidates. Pairwise comparisons revealed greater breed-related divergence at high altitude and a stronger altitude-associated miRNA response in Tibetan pigs than in Yorkshire pigs. The breed-by-altitude interaction analysis identified 94 breed-by-altitude interaction-responsive miRNAs, including 25 not detected by pairwise comparisons. K-means clustering further identified a Tibetan high-altitude-enriched miRNA module whose predicted targets were associated with hypoxia-inducible factor 1 (HIF-1), mechanistic target of rapamycin (mTOR), adrenergic, calcium, and metabolic pathways. Integration with previously published cardiac messenger RNA (mRNA) differential-expression results for high-altitude Tibetan versus Yorkshire pigs, generated from the corresponding biological samples, prioritized 319 anti-correlated miRNA–mRNA pairs involving 19 miRNAs and 224 mRNAs, with ssc-miR-671-5p as the leading network hub. Quantitative real-time polymerase chain reaction (qRT-PCR), correlation analysis, and miRanda prediction prioritized three candidate regulatory pairs: ssc-miR-671-5p–ATP1B2, novel-miR-212–ADCY6, and ssc-miR-296-3p–PFKM. These findings characterize breed-dependent, altitude-associated cardiac miRNA expression patterns and prioritize candidate miRNA–mRNA relationships for future functional investigation.
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BibTeX
@article{li2026breedbyaltitude,
title = {{Breed-by-Altitude Interaction Reveals Cardiac miRNA–mRNA Regulatory Hubs Associated with Hypoxia Adaptation in Tibetan Pigs}},
author = {Pan Li and Wei Cheng and Peng Shang and Zhu Tao and Hao Zhang and Bo Zhang},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209246},
url = {https://www.mdpi.com/1422-0067/27/20/9246},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Breed-by-Altitude Interaction Reveals Cardiac miRNA–mRNA Regulatory Hubs Associated with Hypoxia Adaptation in Tibetan Pigs
AU - Pan Li
AU - Wei Cheng
AU - Peng Shang
AU - Zhu Tao
AU - Hao Zhang
AU - Bo Zhang
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209246
UR - https://www.mdpi.com/1422-0067/27/20/9246
AB - MicroRNAs (miRNAs) are important post-transcriptional regulators of cardiac responses to hypoxia, but how breed and altitude interact to shape cardiac miRNA expression remains unclear. We used a 2 × 2 factorial design involving Tibetan and Yorkshire pigs raised at high (3000 m) or low (100 m) altitude. Small RNA sequencing identified 1104 miRNAs, including 370 known and 734 putative novel miRNA candidates. Pairwise comparisons revealed greater breed-related divergence at high altitude and a stronger altitude-associated miRNA response in Tibetan pigs than in Yorkshire pigs. The breed-by-altitude interaction analysis identified 94 breed-by-altitude interaction-responsive miRNAs, including 25 not detected by pairwise comparisons. K-means clustering further identified a Tibetan high-altitude-enriched miRNA module whose predicted targets were associated with hypoxia-inducible factor 1 (HIF-1), mechanistic target of rapamycin (mTOR), adrenergic, calcium, and metabolic pathways. Integration with previously published cardiac messenger RNA (mRNA) differential-expression results for high-altitude Tibetan versus Yorkshire pigs, generated from the corresponding biological samples, prioritized 319 anti-correlated miRNA–mRNA pairs involving 19 miRNAs and 224 mRNAs, with ssc-miR-671-5p as the leading network hub. Quantitative real-time polymerase chain reaction (qRT-PCR), correlation analysis, and miRanda prediction prioritized three candidate regulatory pairs: ssc-miR-671-5p–ATP1B2, novel-miR-212–ADCY6, and ssc-miR-296-3p–PFKM. These findings characterize breed-dependent, altitude-associated cardiac miRNA expression patterns and prioritize candidate miRNA–mRNA relationships for future functional investigation.
SN - 1422-0067
ER -