{
  "abstract": "Hypoxia-inducible factors (HIFs) are central regulators of cellular adaptation to low oxygen, with a well-documented transition from HIF-1 to HIF-2 signaling during prolonged hypoxia. Here, we investigate the role of a natural antisense transcript of HIF1A, HIF1A-AS2, in modulating this transition in human endothelial cells (ECs). Genome-wide expression profiling revealed a strong hypoxia-induced upregulation of HIF1A-AS2 that coincided with a marked reduction in HIF1A mRNA levels, whereas EPAS1 remained stable. Interestingly, this negative correlation was consistent across multiple EC types and supported by silencing experiments which demonstrated that both HIF-1 and HIF-2 contribute to HIF1A-AS2 induction. Knockdown of HIF1A-AS2 partially restored HIF1A expression and increased HIF-1 protein and functional activity, as evidenced by elevated VEGFA and GLUT1 expression. Genomic analysis identified HIF-1 and HIF-2 binding motifs upstream of HIF1A-AS2, supporting the dual regulation. Furthermore, cancer tissue analysis revealed frequent downregulation of HIF1A-AS2, correlating with elevated HIF1A and EPAS1 levels. These findings suggest that HIF1A-AS2 acts as a hypoxia-responsive regulator that limits HIF-1 signaling and facilitates the HIF isoform switch, and suggests implications for endothelial adaptation, angiogenic signaling, and vascular remodeling under chronic hypoxia.",
  "abstract_shown": true,
  "affiliations": [
    "Uniwersity of Wroclaw"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "A. Barton"
    },
    {
      "name": "A. Wiech-Walow"
    },
    {
      "name": "P. Czechowicz"
    },
    {
      "name": "A. Cabaj"
    },
    {
      "name": "L. Schaefer"
    },
    {
      "name": "J. F. Collawn"
    },
    {
      "affs": [
        0
      ],
      "name": "R. Bartoszewski"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/19383pdyrnhae.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.06.764826",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.11.06.764826v1.full",
  "id": "19383pdyrnhae",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.11.06.764826v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "molecular biology"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.11.06.764826v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-06",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/19383pdyrnhae.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:21:46Z",
      "native_id": "10.64898/2026.11.06.764826",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.11.06.764826v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:molecular biology",
      "subfield": "molecular-biology"
    }
  ],
  "title": "HIF1A-AS2 Regulates Hypoxia-Driven HIF Isoform Switching in Human Endothelial Cells",
  "title_text": "HIF1A-AS2 Regulates Hypoxia-Driven HIF Isoform Switching in Human Endothelial Cells",
  "type": "preprint",
  "updated_at": "2026-11-09T12:21:46Z",
  "url": "https://research.draconitic.com/paper/19383pdyrnhae",
  "venue": "bioRxiv",
  "versions": []
}