Skip to content
DraconiticResearch
Search Sources API
197,768 studies31 sourcesUpdated 10 min ago
Peer-reviewedCC BY 4.0Advanced Science

Metabolic Reprogramming in Glioblastoma Stem Cells Promotes Radiation Resistance Through a H3K18la/USP30/MBOAT2 Axis

  • Zong Miao1
  • Wei Gu2
  • Yimin Ren3
  • Chenfei Lu2
  • Wanzhi Cai2
  • Junnan Lu1
  • Zhongyuan Bao4
  • Yanan Zhou1
  • Rong Li1
  • Ke Jin1
  • Chao Chen1
  • Hongxiang Wang1
2 more authors
  • Lei Xu4
  • Juxiang Chen1
4 affiliations
  1. 1Department of Neurosurgery Changhai Hospital Naval Medical University (Second Military Medical University) Shanghai China
  2. 2Department of Neurosurgery The First Affiliated Hospital of Nanjing Medical University Nanjing China
  3. 3Department of Hematology Huashan Hospital Fudan University Shanghai China
  4. 4Neurovascular Center Changhai Hospital Naval Medical University (Second Military Medical University) Shanghai China
Read full textDOICite

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.

Related

  1. SON-mediated circular RNA suppression promotes PKR signaling and radiation resistance in glioblastoma
    C. A. Harvey, S. K. Dunlap, M. Mohamed +13
    bioRxivPreprintCC BY-NC-NDFull textOncologybioRxiv
  2. KRAS-driven metabolic reprogramming of enhanced MFSD2A-mediated lysophosphatidylcholine scavenging promotes survival and progression of pancreatic ductal adenocarcinoma
    y. chen, C. Haffner, B. Chellakkan Selvanesan +24
    bioRxivPreprintAll rights reservedFull textOncologybioRxiv
  3. L-histidine metabolic reprogramming is associated with imipenem-relebactam resistance in carbapenem-resistant hypervirulent Klebsiella pneumoniae
    Jun Li, Haolan Wang, Yuyao Wang +6
    Scientific ReportsPeer-reviewedCC BY-NC-ND 4.0General medicineCrossref
  4. MiR-22-3p shapes glioblastoma radiation resistance and downregulates the DNA demethylase tumor suppressor TET1
    Claire Loussouarn, Loris Roncali, Amandine Etcheverry +11
    Journal of Experimental and Clinical Cancer ResearchPeer-reviewedCC BYGeneral biologyOncologyHAL
  5. A Novel ACLY Inhibitor Induces Transcriptional and Metabolic Reprogramming to Overcome Tyrosine kinase inhibitor Resistance in Lymphoma
    N. Pattabiraman, C. Lobello, D. Rushmore +9
    bioRxivPreprintAll rights reservedFull textOncologybioRxiv

Cite

BibTeXRIS
BibTeX
@article{miao2026metabolic,
  title = {{Metabolic Reprogramming in Glioblastoma Stem Cells Promotes Radiation Resistance Through a H3K18la/USP30/MBOAT2 Axis}},
  author = {Zong Miao and Wei Gu and Yimin Ren and Chenfei Lu and Wanzhi Cai and Junnan Lu and Zhongyuan Bao and Yanan Zhou and Rong Li and Ke Jin and Chao Chen and Hongxiang Wang and Lei Xu and Juxiang Chen},
  journal = {Advanced Science},
  year = {2026},
  month = aug,
  doi = {10.1002/advs.77044},
  url = {https://doi.org/10.1002/advs.77044},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Metabolic Reprogramming in Glioblastoma Stem Cells Promotes Radiation Resistance Through a H3K18la/USP30/MBOAT2 Axis
AU  - Zong Miao
AU  - Wei Gu
AU  - Yimin Ren
AU  - Chenfei Lu
AU  - Wanzhi Cai
AU  - Junnan Lu
AU  - Zhongyuan Bao
AU  - Yanan Zhou
AU  - Rong Li
AU  - Ke Jin
AU  - Chao Chen
AU  - Hongxiang Wang
AU  - Lei Xu
AU  - Juxiang Chen
PY  - 2026
DA  - 2026/08/12
JO  - Advanced Science
DO  - 10.1002/advs.77044
UR  - https://doi.org/10.1002/advs.77044
AB  - 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.
SN  - 2198-3844
ER  -