{
  "abstract": "Pyroptosis is an immunogenic form of regulated cell death mediated by NLRP3 inflammasome activation, caspase-1, and gasdermin D. Unlike apoptosis, pyroptosis promotes anti-tumor immunity through IL-1β and IL-18 release, making it a promising therapeutic target in hepatocellular carcinoma (HCC). Although the SNHG7/miR-34a/SIRT1 axis has been experimentally linked to NLRP3-dependent pyroptosis, whether it functions as a systems-level regulatory module coordinating the balance between drug resistance and multiple cell-fate outcomes remains unknown. To address this question, we developed a network medicine framework using a Boolean network model integrating drug resistance, senescence, apoptosis, and pyroptosis pathways in HCC. The model was constructed from experimentally validated molecular interactions and independently validated using gain- and loss-of-function perturbation studies that were not used during model construction, demonstrating strong agreement with experimental observations. Our analysis identified a previously unreported MYC-SNHG7-miR-34a double-negative feedback loop, establishing miR-34a as a central regulatory hub controlling cell-fate decisions. Perturbation analysis predicted that SNHG7 inhibition shifts cells from drug resistance toward pyroptosis, identifying restoration of miR-34a activity as a potential strategy to induce immunogenic cell death. These findings provide a systems-level framework for therapeutic targeting of the MYC-SNHG7-miR-34a axis in HCC.",
  "abstract_shown": true,
  "affiliations": [
    "Bioinformatics Multidisciplinary Environment-BioME-Digital Metropole Institute, Federal University of Rio Grande do Norte, Natal 59076-550, RN, Brazil.",
    "Children's Cancer Institute, Porto Alegre 90620-110, RS, Brazil.",
    "Department of Biochemistry, Federal University of Rio Grande do Norte, Natal 59076-550, RN, Brazil.",
    "Departamento de Física, Universidade Federal de Santa Maria, Santa Maria 97105-900, RS, Brazil."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Houemakou Rimaud Djidonou",
      "orcid": "0009-0006-3338-2799"
    },
    {
      "affs": [
        0
      ],
      "name": "Laís de Carvalho Gonçalves",
      "orcid": "0009-0000-5423-592X"
    },
    {
      "affs": [
        0
      ],
      "name": "Djorkaeff O Fontinele",
      "orcid": "0009-0007-1901-9173"
    },
    {
      "affs": [
        1
      ],
      "name": "Daner A Silveira",
      "orcid": "0000-0003-0621-8345"
    },
    {
      "affs": [
        1
      ],
      "name": "Marialva Sinigaglia",
      "orcid": "0000-0002-8324-6860"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Joao Paulo M S Lima",
      "orcid": "0000-0002-6113-8834"
    },
    {
      "affs": [
        3
      ],
      "name": "José Carlos M Mombach",
      "orcid": "0000-0002-6602-3905"
    },
    {
      "affs": [
        0
      ],
      "name": "Shantanu Gupta",
      "orcid": "0000-0001-7110-6564"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9ytnpccce6hf0.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27198441",
  "fulltext_url": "https://europepmc.org/articles/PMC13665239",
  "id": "9ytnpccce6hf0",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://europepmc.org/article/MED/42883693",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1306|Cancer-related molecular mechanisms research"
    ]
  ],
  "openalex": "W7214038889",
  "pdf_url": "https://europepmc.org/articles/PMC13665239?pdf=render",
  "pmcid": "PMC13665239",
  "pmid": "42883693",
  "published": "2026-09-22",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9ytnpccce6hf0.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:16Z",
      "native_id": "MED:42883693",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42883693"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|Cancer-related molecular mechanisms research",
      "subfield": "oncology"
    }
  ],
  "title": "MYC-SNHG7-miR-34a-5p Feedback Loop Orchestrates GSDMD-Dependent Pyroptosis in Hepatocellular Carcinoma.",
  "title_text": "MYC-SNHG7-miR-34a-5p Feedback Loop Orchestrates GSDMD-Dependent Pyroptosis in Hepatocellular Carcinoma.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:16Z",
  "url": "https://research.draconitic.com/paper/9ytnpccce6hf0",
  "venue": "International journal of molecular sciences",
  "versions": []
}