{
  "abstract": "DNA methylation (5-methylcytosine, 5mC) is a major repressive epigenetic mark that can be iteratively oxidized by ten-eleven-translocation (TET) enzymes to 5-hydroxymethylcytosine (5hmC); beyond DNA, modifications of RNA can also affect transcript stability and processing, yet RNA hydroxymethylation remains unexplored in breast cancer (BC). Here, we identify a quantifiable cytoplasmic 5hmC signal in BC cell lines and, more prominently, in human BC tissue, using immunoassays and digital pathology, and confirm with an adapted, RNase-sensitive, RNA-specific ELISA that this signal reflects hydroxymethylation of total RNA and mRNA. Cytoplasmic 5hmC was significantly enriched in triple-negative (ER-/PR-/HER2-) and grade 3 tumors, and correlated with increased cytoplasmic TET2/TET3 in tissue and TET3 upregulation in TCGA. As a leading candidate mechanism, TET3 expression was associated with RNA-processing/spliceosomal transcripts, and TET3 knockdown in three TNBC cell lines reduced a subset of these targets, independently supported across 70 DepMap breast cancer lines.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Surgery and Cancer, Imperial College London, London, United Kingdom"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "name": "J. Wen"
    },
    {
      "name": "L. Del Bel Belluz"
    },
    {
      "name": "S. Ottaviani"
    },
    {
      "name": "F. Poyia"
    },
    {
      "name": "H. Yu"
    },
    {
      "name": "S. Sachdev"
    },
    {
      "name": "L. El Eid"
    },
    {
      "name": "K. Garner"
    },
    {
      "name": "K. Mistry"
    },
    {
      "name": "E. Hayes"
    },
    {
      "name": "N. Moderau"
    },
    {
      "name": "P. C. Chandrasinghe"
    },
    {
      "name": "J. Stebbing"
    },
    {
      "affs": [
        0
      ],
      "name": "B. Cereser"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/87bazsxzjscfj.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.21.760667",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.21.760667v1.full",
  "id": "87bazsxzjscfj",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.21.760667v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "1312|RNA modifications and cancer"
    ]
  ],
  "openalex": "W7223147376",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.21.760667v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-21",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/87bazsxzjscfj.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:28:56Z",
      "native_id": "10.64898/2026.10.21.760667",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.21.760667v2"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Cytoplasmic localization of 5hmC reveals RNA hydroxymethylation in breast cancer",
  "title_text": "Cytoplasmic localization of 5hmC reveals RNA hydroxymethylation in breast cancer",
  "type": "preprint",
  "updated_at": "2026-10-30T12:29:16Z",
  "url": "https://research.draconitic.com/paper/87bazsxzjscfj",
  "venue": "bioRxiv",
  "versions": []
}