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We are analyzing https://www.nature.com/articles/s41418-025-01482-y.

Title:
ATOH8 confers the vulnerability of tumor cells to ferroptosis by repressing SCD expression | Cell Death & Differentiation
Description:
Emerging evidence indicates that transcriptional regulation plays pivotal roles in modulating cellular vulnerability to ferroptosis. However, the intricate mechanisms governing these processes remain poorly understood. In this study, we identify ATOH8, a basic helix-loop-helix (bHLH) transcription factor, as a key player in ferroptosis regulation. ATOH8 is significantly upregulated in tumor cells following treatment with a ferroptosis inducer. Overexpression of ATOH8 increases the susceptibility of tumor cells to ferroptosis, while deletion of ATOH8 promotes ferroptosis evasion. Mechanistically, ATOH8 confers the sensitivity of tumor cells to ferroptosis by suppressing the transcription of stearoyl-CoA desaturase (SCD). Additionally, another bHLH family member, TCF3, is found to functions as a co-factor with ATOH8 by forming a TCF3-ATOH8 transcriptional repressive complex that suppresses SCD transcription. Furthermore, searching for upstream element reveals that EZH2 epigenetically suppresses ATOH8 expression by promoting DNA methylation in the ATOH8 promoter region and increasing the level of H3K27 me3. Importantly, pharmacological inhibition of EZH2 in a combined with a ferroptosis inducer markedly impedes tumor growth both in vitro and in vivo. Collectively, our study elucidates a molecular link between ferroptosis and epigenetic and transcriptional regulation, highlighting the potential of EZH2 and ATOH8 as therapeutic targets for cancer treatment.
Website Age:
30 years and 10 months (reg. 1994-08-11).

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Keywords {πŸ”}

pubmed, google, scholar, ferroptosis, cas, cancer, nature, cell, atoh, article, central, wang, data, cells, access, shanghai, death, ezh, liu, tumor, transcription, content, authors, chen, research, china, wqg, cookies, information, zhang, privacy, expression, xiao, hou, guo, gao, transcriptional, regulation, methylation, nat, biol, sci, medicine, differentiation, march, vulnerability, scd, weiqiang, cellular, dna,

Topics {βœ’οΈ}

nature portfolio privacy policy p62-keap1-nrf2 pathway protects national key research mir-125b-5p represses ferroptosis research physician program advertising basic helix-loop-helix nature social media research institute institutions reprints kdm4a-mediated histone demethylation yu-xiang fang original data file ezh2-mediated slc7a11 upregulation mrna-seq data generated p53-mediated tumour suppression fast gapped-read alignment publishing agreement development program wei-qiang gao springerlink instant access accepted manuscript version permissions stearoyl-coa desaturase development nonapoptotic cell death ferroptotic cell death cell death differ iron-dependent form holds exclusive rights repressing scd expression promoting dna methylation baijun dong privacy published maps srebp transcription factors transcriptional regulator e2a mesenchymal stem cells ezh2 suppresses ferroptosis suppresses scd transcription ren ji hospital nat cell biol distinct ferroptosis pathway kc wong foundation explore content subscription content european economic area

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            name:Shanghai Jiao Tong University
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               name:State Key Laboratory of Systems Medicine for Cancer, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Zhenzhen Wen
      affiliation:
            name:Shanghai Jiao Tong University
            address:
               name:State Key Laboratory of Systems Medicine for Cancer, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Nan Jing
      url:http://orcid.org/0009-0008-8067-9020
      affiliation:
            name:Shanghai Jiao Tong University
            address:
               name:School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Wei-Qiang Gao
      affiliation:
            name:Shanghai Jiao Tong University
            address:
               name:State Key Laboratory of Systems Medicine for Cancer, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
               type:PostalAddress
            type:Organization
            name:Shanghai Jiao Tong University
            address:
               name:School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Baijun Dong
      affiliation:
            name:Shanghai Jiao Tong University
            address:
               name:Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Yu-Xiang Fang
      url:http://orcid.org/0000-0001-6109-2904
      affiliation:
            name:Shanghai Jiao Tong University
            address:
               name:State Key Laboratory of Systems Medicine for Cancer, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:State Key Laboratory of Systems Medicine for Cancer, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
      name:Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
      name:Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
      name:State Key Laboratory of Systems Medicine for Cancer, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
      name:State Key Laboratory of Systems Medicine for Cancer, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
      name:State Key Laboratory of Systems Medicine for Cancer, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
      name:State Key Laboratory of Systems Medicine for Cancer, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
      name:School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China
      name:State Key Laboratory of Systems Medicine for Cancer, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
      name:School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China
      name:Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
      name:State Key Laboratory of Systems Medicine for Cancer, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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