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

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.

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.

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.