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Transcriptomic landscape of human circular RNAs: unveiling molecular mechanisms in high-altitude adaptation
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DOI：10.3389/fgene.2026.1823611.png)
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Abstract
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High altitude (HA) is associated with environmental stress and low oxygen levels; and HA adaptation varies among populations. This study aimed to explore HA adaptation-related circular RNAs (circRNAs) and their transcriptomic profiles. We performed high-throughput analysis on male individuals from three populations at different altitudes and identified gene copy number variations (CNVs) and numerous differentially expressed circRNAs (DEcircRNAs) via pairwise comparisons. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the parent genes of DEcircRNAs were enriched in biological regulation and the hypoxia-inducible factor-1 (HIF-1) signaling pathway. Five key DEcircRNAs (hsa_circ_0044526; hsa_circ_0022498; hsa_circ_0044534; hsa_circ_0044520; and hsa_circ_0026102) interacting with RBPs (argonaute 2 protein (AGO2) and eukaryotic translation initiation factor 4A3 (EIF4A3)) were identified. Their expression increased with altitude; with the highest expression observed at 3; 000 m). Overexpression of HIF-1 was positively correlated with the upregulated expression of the five circRNAs in human endothelial cells; offering preliminary correlative evidence for investigating hypoxia-associated transcriptional links underlying high-altitude adaptation. Collectively; these DEcircRNAs may contribute to HIF-1-mediated HA adaptive metabolism.
Keywords:
high altitude
hypoxia-inducible factor-1
circular RNAs
high-altitude adaptation
argonaute 2 protein
eukaryotic translation initiation factor 4A3
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