在胶质母细胞瘤进展过程中，IDO1通过调节fto介导的m6A甲基化和SLC7A11 mRNA的稳定性来抑制铁凋亡。

IF 10.4 2区生物学 Q1 CELL BIOLOGY Cell Death Discovery Pub Date : 2025-01-25 DOI:10.1038/s41420-025-02293-3

Qianting Tian, Guixue Dan, Xuyan Wang, Jiamei Zhu, Chaochun Chen, Dekun Tang, Ziming Wang, Dan Chen, Shan Lei, Chao Yang, Houmei Wang, Bing Guo, Bangming Jin, Tengxiang Chen, Lei Tang

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引用次数: 0

摘要

吲哚胺2,3 -双加氧酶1 （IDO1）被认为是一种参与色氨酸分解代谢的酶，具有免疫抑制能力。本研究旨在探讨IDO1对多形性胶质母细胞瘤（GBM）细胞的影响。在这里，我们发现IDO1的表达在胶质瘤患者中显著增加，并与GBM进展相关。IDO1过表达可抑制GBM细胞凋亡，减少ROS和过氧化脂质生成。IDO1的表达通过fto依赖的m6A甲基化增加了SLC7A11 mRNA的稳定性。在机制上，IDO1促进了AhR的表达和核易位，从而促进了FTO基因启动子区AhR的募集，并负向调控其转录。这些发现表明，IDO1通过IDO1- ahr - fto轴介导的m6A甲基化机制，抑制slc7a11依赖性铁凋亡，从而促进GBM的进展。

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IDO1 inhibits ferroptosis by regulating FTO-mediated m6A methylation and SLC7A11 mRNA stability during glioblastoma progression.

Indoleamine 2, 3-dioxygenase 1 (IDO1) has been recognized as an enzyme involved in tryptophan catabolism with immunosuppressive ability. This study determined to investigate the impact of IDO1 on glioblastoma multiforme (GBM) cells. Here, we showed that the expression of IDO1 was markedly increased in patients with glioma and associated with GBM progression. IDO1 overexpression suppressed ferroptotic cell death, reduced ROS and lipid peroxide generation in GBM cells. IDO1 expression increased the SLC7A11 mRNA stability through FTO-dependent m6A methylation. Mechanistically, IDO1 promoted the AhR expression and nuclear translocation, thus facilitating AhR recruitment at the promoter regions of FTO gene and negatively regulating its transcription. These findings demonstrate that IDO1 facilitates GBM progression by inhibiting SLC7A11-dependent ferroptosis through an IDO1-AhR-FTO axis-mediated m6A methylation mechanism.

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来源期刊

Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

8.30

自引率

1.40%

发文量

468

审稿时长

9 weeks

期刊介绍： Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary. Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.