Evidence map›Paper›PMID 41338221›Full record

ArticleCell reports. Medicine2025

Targeting TET3 suppresses group 3 medulloblastoma stemness and progression via impairing hypomethylation of Otx2 super-enhancer.

Xuan Chen, Ziwei Wang, Yan Song, Yu Su, Yahui Zhao, Jiankang Li, Wei Wang, Jiao Zhang, Craig Daniels, Xiaochong Wu and 30 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. From developmental origins to relapse: molecular and therapeutic insights in medulloblastoma.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

40 authors.

Xuan ChenCollege of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; BGI Research, Chongqing 401329, China; BGI Research, Shenzhen, Guangdong 518083, China.
Ziwei WangBGI Research, Chongqing 401329, China; BGI Research, Shenzhen, Guangdong 518083, China.
Yan SongState Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 10029, China.
Yu SuSchool of Public Health, Capital Medical University, Beijing 100069, China.
Yahui ZhaoDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China; China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China; Beijing Neurosurgical Institute, Beijing 100070, China.
Jiankang LiBGI Research, Chongqing 401329, China; BGI Research, Shenzhen, Guangdong 518083, China; Computer Science Department, City University of Hong Kong, Kowloon, Hong Kong, China; State Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Shenzhen 518083, China.
Wei WangLaboratory of Tumor Immunology, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.
Jiao ZhangCancer and Hematology Center, Texas Children's Hospital, Houston, TX 77002, USA; Department of Pediatrics-Hematology/Oncology and Neurosurgery, Baylor College of Medicine, Houston, TX 77002, USA; The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1, Canada; The Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 1, Canada.
Craig DanielsCancer and Hematology Center, Texas Children's Hospital, Houston, TX 77002, USA; Department of Pediatrics-Hematology/Oncology and Neurosurgery, Baylor College of Medicine, Houston, TX 77002, USA; The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1, Canada; The Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 1, Canada.
Xiaochong WuCancer and Hematology Center, Texas Children's Hospital, Houston, TX 77002, USA; Department of Pediatrics-Hematology/Oncology and Neurosurgery, Baylor College of Medicine, Houston, TX 77002, USA; The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1, Canada; The Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 1, Canada.
Olivier SaulnierGenomics and Development of Childhood Cancers Lab, Inserm U1330, Institut Curie, PSL University, SiREDO Oncology Center, Paris, France.
Yanan WangState Key Laboratory of Common Mechanism Research for Major Diseases, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Fei LiuDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China; Department of Radiotherapy, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
Kaiwen DengDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China; Department of Radiotherapy, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
Dongming HanCollege of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; BGI Research, Chongqing 401329, China; BGI Research, Shenzhen, Guangdong 518083, China.
Zijia LiuCollege of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; BGI Research, Chongqing 401329, China; BGI Research, Shenzhen, Guangdong 518083, China.
Meiyu LiCollege of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; BGI Research, Chongqing 401329, China; BGI Research, Shenzhen, Guangdong 518083, China.
Liam D HendrikseThe Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1, Canada; The Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 1, Canada.
Alexandra RasnitsynThe Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1, Canada; The Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 1, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1, Canada.
Evan Y WangThe Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1, Canada; The Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 1, Canada.
Dongyang WangDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
Zhaoyang FengDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China; Department of Radiotherapy, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
Yanong LiDepartment of Radiotherapy, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
Zitong ZhaoState Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Hongyu YuanInstitute of Basic Medicine, School of Medicine, Tsinghua University, Beijing 100084, China.
Youliang SunInstitute of Basic Medicine, School of Medicine, Tsinghua University, Beijing 100084, China.
Yifei JiangUniversity of Michigan-Shanghai Jiao Tong University Joint Institute, Shanghai Jiao Tong University, Shanghai 200240, China; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
Yanfeng ShiChina National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
Tao YangChina National GeneBank, BGI-Research, Shenzhen, Guangdong 518083, China.
Xueling QiDepartment of Neuro-Pathology, Sanbo Brain Hospital Capital Medical University, Beijing 100093, China.
Yong HouCollege of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; BGI Research, Shenzhen, Guangdong 518083, China.
Chunde LiDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
Yong-Qiang LiuResearch Center of Chinese Herbal Resource Science and Engineering, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China.
Yu TianSchool of Public Health, Capital Medical University, Beijing 100069, China; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Shuaicheng LiComputer Science Department, City University of Hong Kong, Kowloon, Hong Kong, China.
Xiaoguang QiuDepartment of Medical Biophysics, University of Toronto, Toronto, ON M5G 1, Canada.
Michael D TaylorCancer and Hematology Center, Texas Children's Hospital, Houston, TX 77002, USA; Department of Pediatrics-Hematology/Oncology and Neurosurgery, Baylor College of Medicine, Houston, TX 77002, USA; The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1, Canada; The Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 1, Canada.
Guo Liang LiState Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 10029, China. Electronic address: glli@buct.edu.cn.
Tao JiangDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China; China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China; Beijing Neurosurgical Institute, Beijing 100070, China. Electronic address: zacharytaojiang@163.com.
Hailong LiuChina National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China; Beijing Neurosurgical Institute, Beijing 100070, China; Department of Radiotherapy, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China; Chinese Institute for Medical Research, Beijing 100069, China. Electronic address: liuhailonger@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Medulloblastoma (MB), particularly Group_3 (G3-MB), remains the most aggressive subgroup due to strong stemness and therapeutic resistance. Through genome-wide DNA methylation and transcriptomic analysis of human MB samples, we identify enhancer hypomethylation as a key feature sustaining G3-MB stemness and tumor progression. Notably, hypomethylation of the Otx2 super-enhancer (SE) is a prognostic marker and potential therapeutic target for G3-MB patients. We demonstrate that disrupting Otx2 SE activity effectively reduces tumor growth in vivo, highlighting its critical role in G3-MB maintenance. TET3, recruited by OTX2, demethylates the Otx2 SE, promoting chromatin opening and sustaining tumor proliferation and stemness. To translate these findings into therapy, we develop a liposomal nanoparticle (LNP)-based delivery system for siTET3 or a cytosine-based inhibitor of TET3, achieving significant tumor-suppressive effect in a patient-derived orthotopic xenograft model of G3-MB. Our study provides the targeted approach for Otx2-driven G3-MB and introduces LNP-based epigenetic therapy as a promising low-toxicity strategy.

Indexed as

Cerebellar NeoplasmsDioxygenasesDNA MethylationMedulloblastomaNeoplastic Stem CellsOtx Transcription FactorsAnimalsCell Line, TumorCell ProliferationDisease ProgressionFemaleGene Expression Regulation, NeoplasticHumansMiceXenograft Model Antitumor AssaysDioxygenasesOTX2 protein, humanOtx Transcription FactorsDNA hypomethylationmedulloblastomaOtx2TET3treatment

Identifiers

PMID41338221
PMCPMC12765832

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.