{
  "abstract": "Ferroptosis is a unique form of regulated cell death characterized by iron-dependent lipid peroxidation. Although the molecular details of ferroptosis regulation have been widely explored, the contributions of short non-coding RNAs (ncRNAs) to ferroptosis regulation, other than miRNAs, remain poorly understood. Here, we identified vault RNA1-1 (vtRNA1-1) as a previously unrecognized short ncRNA regulator of ferroptosis in hepatocellular carcinoma (HCC) cells. vtRNA1-1 expression was upregulated by ferroptosis inducers and exhibited strong negative correlation with ferroptosis sensitivity, thus protecting cells from ferroptosis. vtRNA1-1 levels were elevated in selected ferroptosis-resistant cells, while its depletion reversed the phenotype thus resensitizing these cells to ferroptosis. These findings suggested a contribution of vtRNA1-1 to both intrinsic and acquired ferroptosis resistance. Mechanistically, we uncovered that increased oxidative stress, which potentiates lipid peroxidation, specifically induced expression of the vtRNA1-1 paralog in an NF-κB dependent manner. Elevated vtRNA1-1 levels suppressed NF-κB-mediated pro-oxidant gene expression, thereby limiting reactive oxygen species (ROS) accumulation and alleviating oxidative stress. Taken together, oxidative stress-inducible vtRNA1-1 governs redox balance by forming a reciprocal regulatory loop with NF-κB and this loop determines ferroptosis susceptibility by adjusting basal ROS levels. Our findings provide unprecedented insights into the regulation of redox homeostasis in HCC cells mediated by a short ncRNA and uncovered vtRNA1-1 as a potential therapeutic target for overcoming ferroptosis resistance in liver cancer.",
  "abstract_shown": true,
  "affiliations": [
    "Department for Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, Bern, 3012, Switzerland.",
    "Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital and University of Bern, Bern, 3010, Switzerland.",
    "Department for Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, Bern, 3012, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, 3012, Switzerland.",
    "Department for Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, Bern, 3012, Switzerland. Electronic address: norbert.polacek@unibe.ch."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "EunBin Kong"
    },
    {
      "affs": [
        1
      ],
      "name": "Daniel Sanchez-Taltavull"
    },
    {
      "affs": [
        0
      ],
      "name": "Carolina Oliveira-Rizzo"
    },
    {
      "affs": [
        2
      ],
      "name": "Anastasiia Suspitsyna"
    },
    {
      "affs": [
        1
      ],
      "name": "Deborah Stroka"
    },
    {
      "affs": [
        3
      ],
      "name": "Norbert Polacek",
      "orcid": "0000-0001-5317-3990"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bte9defz8vsvj.bib",
  "cited_by": 0,
  "doi": "10.1016/j.redox.2026.104439",
  "fulltext_url": "https://europepmc.org/articles/PMC13693114",
  "id": "bte9defz8vsvj",
  "issns": [
    "2213-2317"
  ],
  "landing_url": "https://europepmc.org/article/MED/42880018",
  "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",
      "2740|Ferroptosis and cancer prognosis"
    ]
  ],
  "openalex": "W7221636178",
  "pdf_url": "https://europepmc.org/articles/PMC13693114?pdf=render",
  "pmcid": "PMC13693114",
  "pmid": "42880018",
  "published": "2026-10-13",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bte9defz8vsvj.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:00Z",
      "native_id": "MED:42880018",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42880018"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "journal-openalex:1312|Redox biology and oxidative stress",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Stress-induced vtRNA1-1 modulates redox homeostasis and ferroptosis susceptibility in hepatocellular carcinoma cells.",
  "title_text": "Stress-induced vtRNA1-1 modulates redox homeostasis and ferroptosis susceptibility in hepatocellular carcinoma cells.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:00Z",
  "url": "https://research.draconitic.com/paper/bte9defz8vsvj",
  "venue": "Redox biology",
  "versions": []
}