{
  "abstract": "High-grade serous ovarian carcinoma (HGSOC), the most lethal subtype of ovarian cancer, is often diagnosed at advanced stages and remains associated with poor clinical outcome. In this study, we identify a critical oncogenic role of the RNA methyltransferase METTL3 and the N6-methyladenosine (m6A) RNA modification pathway in HGSOC. Suppression of METTL3, either genetically or pharmacologically, and depletion of its binding partner METTL14 impair ovarian cancer proliferation and tumor progression. Mechanistically, we show that METTL3-mediated m6A deposition enhances the translation of DNA methyltransferase 1 (DNMT1), the primary maintenance DNA methyltransferase responsible for preserving genome-wide methylation patterns and silencing tumor suppressor genes. Pharmacological inhibition of DNMT1 induces widespread DNA hypomethylation and up-regulation of the tumor suppressors TNFAIP3 and FBXO32. Consistently, METTL3 suppression reduces DNMT1 abundance and derepresses TNFAIP3 and FBXO32 expression. Knockdown and rescue studies further reveal that DNMT1 primarily mediates METTL3-dependent regulation of cell migration, whereas the antiproliferative effects of METTL3 suppression are likely driven by additional downstream targets. Collectively, these findings identify the m6A-METTL3-DNMT1 axis as a mechanistic link between RNA and DNA methylation pathways and a potential therapeutic vulnerability in HGSOC.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Molecular Biology, Umeå University, SE-901 85 Umeå, Sweden.",
    "Wallenberg Centre for Molecular Medicine, Umeå University, SE-901 85 Umeå, Sweden.",
    "Cancer Research Program, Hospital del Mar Medical Research Institute (HMRI), Barcelona, Spain.",
    "Cancer Epigenetics Group, Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain.",
    "Department of Biosciences, Faculty of Science, Technology and Engineering, University of Vic-Central University of Catalonia (UVic-UCC), Vic, Barcelona, Catalonia, Spain.",
    "Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Madrid, Spain.",
    "Genomics Unit, Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain.",
    "Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, 38123 Trento, Italy.",
    "Department of Medical Biosciences, Umeå University, SE-901 85 Umeå, Sweden.",
    "Department of Chemistry, The University of Chicago, Chicago, IL 60637, USA.",
    "Department of Molecular Biology and Genetics, University of Extremadura, 06071 Badajoz, Spain.",
    "Cancer Epigenetics Group, Sant Pau Research Institute (IRSantPau), Barcelona, Catalonia, Spain.",
    "Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain.",
    "Physiological Sciences Department, School of Medicine and Health Sciences, University of Barcelona (UB), Barcelona, Catalonia, Spain."
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Kanchan Kumari",
      "orcid": "0000-0001-7546-4174"
    },
    {
      "affs": [
        2
      ],
      "name": "Iván Pérez-Núñez",
      "orcid": "0000-0002-2907-1991"
    },
    {
      "affs": [
        3,
        4,
        5
      ],
      "name": "Aleix Noguera Castells",
      "orcid": "0000-0001-7436-6513"
    },
    {
      "affs": [
        6
      ],
      "name": "Raquel Pluvinet",
      "orcid": "0000-0002-4955-8238"
    },
    {
      "affs": [
        7
      ],
      "name": "Carlos Peula",
      "orcid": "0009-0005-4991-6372"
    },
    {
      "affs": [
        8
      ],
      "name": "Annika Patthey"
    },
    {
      "affs": [
        1,
        8
      ],
      "name": "Ghazala Naz Khan"
    },
    {
      "affs": [
        9
      ],
      "name": "Kinga Pajdzik"
    },
    {
      "affs": [
        10
      ],
      "name": "Ángel-Carlos Román"
    },
    {
      "affs": [
        6
      ],
      "name": "Erik Dassi",
      "orcid": "0000-0003-4487-0449"
    },
    {
      "affs": [
        9
      ],
      "name": "Chuan He",
      "orcid": "0000-0003-4319-7424"
    },
    {
      "affs": [
        8
      ],
      "name": "Eva Lundin",
      "orcid": "0009-0005-4461-3719"
    },
    {
      "affs": [
        5,
        11,
        12,
        13
      ],
      "name": "Manel Esteller",
      "orcid": "0000-0003-4490-6093"
    },
    {
      "affs": [
        2
      ],
      "name": "Toni Celià-Terrassa",
      "orcid": "0000-0002-0615-8744"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Francesca Aguilo",
      "orcid": "0000-0002-2374-2045"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b69na1b1z6td1.bib",
  "cited_by": 0,
  "doi": "10.1126/sciadv.aec2297",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13733898/",
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  "issns": [
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  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Biomedicine and Life Sciences"
    ],
    [
      "heading",
      "Cancer"
    ],
    [
      "heading",
      "Molecular Biology"
    ],
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      "heading",
      "Research Article"
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      "heading",
      "SciAdv r-articles"
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  "openalex": null,
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  "pmcid": "PMC13733898",
  "pmid": "42981409",
  "published": "2026-11-04",
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "ris": "https://research.draconitic.com/paper/b69na1b1z6td1.ris",
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "heading:Molecular Biology",
      "subfield": "molecular-biology"
    },
    {
      "field": "medicine",
      "origin": "heading:Cancer",
      "subfield": "oncology"
    }
  ],
  "title": "METTL3-mediated m6A modification of DNMT1 enhances ovarian cancer progression",
  "title_text": "METTL3-mediated m6A modification of DNMT1 enhances ovarian cancer progression",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:23:35Z",
  "url": "https://research.draconitic.com/paper/b69na1b1z6td1",
  "venue": "Science Advances",
  "versions": []
}