{
  "abstract": "Mesenchymal glioma stem cells (MES GSCs) are closely associated with glioblastoma radioresistance, yet the mechanisms linking MES‐state maintenance to ferroptosis resistance remain incompletely defined. Here, we show that MES GSCs exhibit enhanced glycolytic activity and lactate production, driven in part by MES‐associated transcriptional regulators that promote LDHA expression. LDHA‐derived lactate induces p300‐dependent H3K18 lactylation, which enhances USP30 transcription. USP30 subsequently stabilizes the lipid‐remodeling enzyme MBOAT2 by limiting its ubiquitination, leading to phosphatidylethanolamine remodeling toward ferroptosis‐resistant PE‐MUFA species. Disruption of this LDHA–H3K18la–USP30–MBOAT2 axis by LDHA inhibition, impaired H3K18 lactylation, USP30 inhibition, or MBOAT2 depletion increases lipid peroxidation, promotes ferroptosis, and sensitizes MES GSCs to irradiation. Lipid rescue experiments further identify PE‐MUFA remodeling as a functional mediator of MBOAT2‐dependent ferroptosis resistance. In intracranial xenografts, combined targeting of glycolysis and USP30 enhances radiotherapeutic efficacy without obvious treatment‐associated body weight loss under the tested conditions. These findings reveal a metabolic–epigenetic–lipid remodeling circuit that protects MES GSCs from ferroptosis and promotes radioresistance.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neurosurgery Changhai Hospital Naval Medical University (Second Military Medical University) Shanghai China",
    "Department of Neurosurgery The First Affiliated Hospital of Nanjing Medical University Nanjing China",
    "Department of Hematology Huashan Hospital Fudan University Shanghai China",
    "Neurovascular Center Changhai Hospital Naval Medical University (Second Military Medical University) Shanghai China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Zong Miao"
    },
    {
      "affs": [
        1
      ],
      "name": "Wei Gu"
    },
    {
      "affs": [
        2
      ],
      "name": "Yimin Ren"
    },
    {
      "affs": [
        1
      ],
      "name": "Chenfei Lu"
    },
    {
      "affs": [
        1
      ],
      "name": "Wanzhi Cai"
    },
    {
      "affs": [
        0
      ],
      "name": "Junnan Lu"
    },
    {
      "affs": [
        3
      ],
      "name": "Zhongyuan Bao"
    },
    {
      "affs": [
        0
      ],
      "name": "Yanan Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Rong Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Ke Jin"
    },
    {
      "affs": [
        0
      ],
      "name": "Chao Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Hongxiang Wang"
    },
    {
      "affs": [
        3
      ],
      "name": "Lei Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Juxiang Chen",
      "orcid": "0000-0002-5171-9707"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6j06a52m26k7r.bib",
  "cited_by": 0,
  "doi": "10.1002/advs.77044",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13464552/",
  "id": "6j06a52m26k7r",
  "issns": [
    "2198-3844"
  ],
  "landing_url": "https://doi.org/10.1002/advs.77044",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2740|Ferroptosis and cancer prognosis"
    ]
  ],
  "openalex": "W7202247220",
  "pdf_url": null,
  "pmcid": "PMC13464552",
  "pmid": "42584947",
  "published": "2026-08-12",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/6j06a52m26k7r.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T12:23:12Z",
      "native_id": "PMC13464552",
      "source": "pmc",
      "url": "https://doi.org/10.1002/advs.77044"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Ferroptosis and cancer prognosis",
      "subfield": "general"
    }
  ],
  "title": "Metabolic Reprogramming in Glioblastoma Stem Cells Promotes Radiation Resistance Through a H3K18la/USP30/MBOAT2 Axis",
  "title_text": "Metabolic Reprogramming in Glioblastoma Stem Cells Promotes Radiation Resistance Through a H3K18la/USP30/MBOAT2 Axis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:20:30Z",
  "url": "https://research.draconitic.com/paper/6j06a52m26k7r",
  "venue": "Advanced Science",
  "versions": []
}