{
  "abstract": "Background\n\nRadiotherapy remains a cornerstone of breast cancer treatment, yet radioresistance limits its efficacy. miR-206 acts as a tumor suppressor by inhibiting SIRT1 and stabilizing p53. However, how these molecular components are organized within larger regulatory networks, and whether such network-level hubs can be therapeutically prioritized, remains unclear.Results\n\nNetwork modeling predicted a previously unrecognized double-negative feedback loop (miR-206 ⊣ SIRT1 ⊣ p53 → miR-206) that functions as a predicted bistable switch, driving mutually exclusive commitment to either a radiosensitive (apoptotic) or a radioresistant (proliferative) fate. Monte Carlo simulations revealed that opposite perturbations of this circuit consistently drove the system toward the corresponding stable attractor. Edge disruption analysis identified the miR-206/SIRT1 and p53/miR-206 interactions as essential for maintaining bistability, while ATM exerted p53-dependent context-specific effects. Model predictions were consistent with independent experimental observations that miR-206 overexpression suppresses SIRT1, enhances p53 acetylation, and increases radiosensitivity.Conclusions\n\nThis network medicine framework identifies the miR-206/SIRT1/p53 bistable switch as a key regulatory module governing cell-fate decisions in breast cancer radioresistance. The model provides a systems-level platform for prioritizing experimentally testable therapeutic strategies to overcome radioresistance.",
  "abstract_shown": true,
  "affiliations": [
    "Bioinformatics Multidisciplinary Environment-BioME - Digital Metropole Institute, Federal University of Rio Grande Do Norte, Natal, RN, 59076550, Brazil.",
    "Department of Biophysics and Pharmacology, Federal University of Rio Grande Do Norte, Natal, RN, 59076550, Brazil.",
    "Department of Biochemistry, Federal University of Rio Grande Do Norte, Natal, RN, 59076550, Brazil.",
    "Bioinformatics Multidisciplinary Environment-BioME - Digital Metropole Institute, Federal University of Rio Grande Do Norte, Natal, RN, 59076550, Brazil. shantanu.gupta@imd.ufrn.br."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Djorkaeff O Fontinele"
    },
    {
      "affs": [
        1
      ],
      "name": "Klaus A R Reiniger"
    },
    {
      "affs": [
        2
      ],
      "name": "Arthur H D Azevedo"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Joao Paulo M S Lima"
    },
    {
      "affs": [
        3
      ],
      "name": "Shantanu Gupta"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e31x9s9105mzj.bib",
  "cited_by": 0,
  "doi": "10.1186/s12859-026-06592-z",
  "fulltext_url": "https://europepmc.org/articles/PMC13726001",
  "id": "e31x9s9105mzj",
  "issns": [
    "1471-2105"
  ],
  "landing_url": "https://europepmc.org/article/MED/42968013",
  "language": "eng",
  "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": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "1306|MicroRNA in disease regulation"
    ]
  ],
  "openalex": "W7172402364",
  "pdf_url": "https://europepmc.org/articles/PMC13726001?pdf=render",
  "pmcid": "PMC13726001",
  "pmid": "42968013",
  "published": "2026-08-04",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/e31x9s9105mzj.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T15:20:54Z",
      "native_id": "MED:42968013",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42968013"
    },
    {
      "first_seen": "2026-11-05T12:22:26Z",
      "native_id": "PMC13726001",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s12859-026-06592-z"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|MicroRNA in disease regulation",
      "subfield": "oncology"
    }
  ],
  "title": "miR-206 orchestrates breast cancer radiosensitivity through a SIRT1/p53 feedback loop: a network medicine modelling study.",
  "title_text": "miR-206 orchestrates breast cancer radiosensitivity through a SIRT1/p53 feedback loop: a network medicine modelling study.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:22:03Z",
  "url": "https://research.draconitic.com/paper/e31x9s9105mzj",
  "venue": "BMC bioinformatics",
  "versions": []
}