{
  "abstract": "Glioblastoma (GBM) exhibits extensive loss of circular RNAs (circRNAs), yet the mechanisms driving this depletion and its functional consequences remain unclear. Here, we identify the splicing co-factor SON as a previously unrecognized suppressor of circRNA biogenesis in GBM. CircRNA sequencing revealed widespread increases in circRNA abundance following SON knockdown. Conversely, elevated SON expression in GBM, with further increases in radiation-resistant models, was associated with widespread circRNA loss, including reduced expression of circUSP1 and circSUCO. SON knockdown increased circRNA abundance and attenuated activation of the dsRNA-responsive kinase PKR and downstream NF{kappa}B signaling, whereas radiation-resistant GBM cells exhibited enhanced PKR/NF{kappa}B activation that was attenuated by SON depletion. Importantly, overexpression of the SON-suppressed circRNAs circUSP1 and circSUCO reduced PKR activation and selectively decreased clonogenic survival following irradiation in radiation-resistant GBM cells, with little effect on parental cells. Together, these findings identify a previously unrecognized SON/circRNA/PKR regulatory pathway linking RNA processing to acquired radiation resistance in GBM and highlight specific PKR-inhibitory circRNAs as potential therapeutic tools for resensitizing radiation-resistant GBM to radiotherapy.",
  "abstract_shown": true,
  "affiliations": [
    "University of Alabama at Birmingham"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "name": "C. A. Harvey"
    },
    {
      "name": "S. K. Dunlap"
    },
    {
      "name": "M. Mohamed"
    },
    {
      "name": "E. Kudaravalli"
    },
    {
      "name": "A. Elkholy"
    },
    {
      "name": "L. Gehrs"
    },
    {
      "name": "S. Zakakhosravi"
    },
    {
      "name": "B. Park"
    },
    {
      "name": "K. W. Min"
    },
    {
      "name": "J. M. Murphy"
    },
    {
      "name": "O. Iwaloye"
    },
    {
      "name": "S. Osuka"
    },
    {
      "name": "S.-T. S. Lim"
    },
    {
      "name": "C. D. Willey"
    },
    {
      "name": "E. K. Flemington"
    },
    {
      "affs": [
        0
      ],
      "name": "E.-Y. E. Ahn"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d8n4mhpmvzf2n.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.28.755153",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.28.755153v1.full",
  "id": "d8n4mhpmvzf2n",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.28.755153v1",
  "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",
      "cancer biology"
    ],
    [
      "openalex",
      "1312|Circular RNAs in diseases"
    ]
  ],
  "openalex": "W7214700929",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.28.755153v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-28",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/d8n4mhpmvzf2n.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:11Z",
      "native_id": "10.64898/2026.09.28.755153",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.28.755153v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "SON-mediated circular RNA suppression promotes PKR signaling and radiation resistance in glioblastoma",
  "title_text": "SON-mediated circular RNA suppression promotes PKR signaling and radiation resistance in glioblastoma",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:11Z",
  "url": "https://research.draconitic.com/paper/d8n4mhpmvzf2n",
  "venue": "bioRxiv",
  "versions": []
}