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Background <p>The Tibetan pig, an indigenous breed adapted to plateau environments in China, exhibits remarkable tolerance to extreme high-altitude conditions. Recent studies have highlighted the pivotal role of non-coding RNAs (ncRNAs) in regulating hypoxic adaptation. However, the complex regulatory network involving mRNAs and ncRNAs that mediate this adaptation in Tibetan pigs remains poorly understood.</p> Results <p>We performed whole-transcriptome sequencing to analyze expression profiles of mRNAs, lncRNAs, and miRNAs in heart tissues of Tibetan pigs (TH) and Yorkshire pigs (YH) at high altitude. We identified 795 differentially expressed lncRNAs (DE lncRNAs), 149 differentially expressed miRNAs (DE miRNAs), and 2,206 differentially expressed mRNAs (DE mRNAs) between TH and YH. Functional enrichment analysis showed that target genes of DE miRNAs, DE lncRNAs, and DE mRNAs significantly enriched pathways related to hypoxic adaptation, including Dilated Cardiomyopathy (DCM) and Hypertrophic Cardiomyopathy (HCM). We constructed a competing endogenous RNA (ceRNA) regulatory network comprising 8 DE lncRNAs, 37 DE miRNAs, and 7 DE mRNAs. Notably, we validated the MSTRG.19853.1/ssc-miR-361-3p/<i>NPPA</i> axis, a candidate regulator of cardiac adaptation, using quantitative real-time PCR (qRT-PCR) and dual-luciferase reporter assays.</p> Conclusion <p>Our findings elucidate comprehensive RNA expression profiles and ncRNA-mRNA interactions underlying hypoxic adaptation in Tibetan pig hearts compared to Yorkshire pigs at high altitude. The MSTRG.19853.1/ssc-miR-361-3p/<i>NPPA</i> axis represents a promising candidate for regulating cardiac adaptation under hypoxia, pending in vivo validation. These insights enhance our understanding of the genetic mechanisms driving high-altitude adaptation in Tibetan pigs, offering a foundation for comparative studies of hypoxic resilience in plateau mammals.</p> Graphical Abstract <p>The model of MSTRG.19853.1/ssc-miR-361-3p/<i>NPPA</i> axis for regulating hypoxia adaptation in Tibetan and Yorkshire pigs.</p> <p></p>

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Comprehensive transcriptome analysis reveals MSTRG.19853.1/ssc-miR-361-3p/NPPA axis is related to hypoxic adaptation in Tibetan pigs

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月1日

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  • Pan Li,
  • Wei Cheng,
  • Zhandui Pubu,
  • Peng Shang,
  • Hao Zhang,
  • Bo Zhang

摘要

Background

The Tibetan pig, an indigenous breed adapted to plateau environments in China, exhibits remarkable tolerance to extreme high-altitude conditions. Recent studies have highlighted the pivotal role of non-coding RNAs (ncRNAs) in regulating hypoxic adaptation. However, the complex regulatory network involving mRNAs and ncRNAs that mediate this adaptation in Tibetan pigs remains poorly understood.

Results

We performed whole-transcriptome sequencing to analyze expression profiles of mRNAs, lncRNAs, and miRNAs in heart tissues of Tibetan pigs (TH) and Yorkshire pigs (YH) at high altitude. We identified 795 differentially expressed lncRNAs (DE lncRNAs), 149 differentially expressed miRNAs (DE miRNAs), and 2,206 differentially expressed mRNAs (DE mRNAs) between TH and YH. Functional enrichment analysis showed that target genes of DE miRNAs, DE lncRNAs, and DE mRNAs significantly enriched pathways related to hypoxic adaptation, including Dilated Cardiomyopathy (DCM) and Hypertrophic Cardiomyopathy (HCM). We constructed a competing endogenous RNA (ceRNA) regulatory network comprising 8 DE lncRNAs, 37 DE miRNAs, and 7 DE mRNAs. Notably, we validated the MSTRG.19853.1/ssc-miR-361-3p/NPPA axis, a candidate regulator of cardiac adaptation, using quantitative real-time PCR (qRT-PCR) and dual-luciferase reporter assays.

Conclusion

Our findings elucidate comprehensive RNA expression profiles and ncRNA-mRNA interactions underlying hypoxic adaptation in Tibetan pig hearts compared to Yorkshire pigs at high altitude. The MSTRG.19853.1/ssc-miR-361-3p/NPPA axis represents a promising candidate for regulating cardiac adaptation under hypoxia, pending in vivo validation. These insights enhance our understanding of the genetic mechanisms driving high-altitude adaptation in Tibetan pigs, offering a foundation for comparative studies of hypoxic resilience in plateau mammals.

Graphical Abstract

The model of MSTRG.19853.1/ssc-miR-361-3p/NPPA axis for regulating hypoxia adaptation in Tibetan and Yorkshire pigs.