IDO1 inhibits ferroptosis by regulating FTO-mediated m6A methylation and SLC7A11 mRNA stability during glioblastoma progression
Abstract 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 i...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2025-01-01
|
| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-025-02293-3 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832586078476828672 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Qianting Tian |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-a5b8e3e0210e484c983f29faca411d6a |
| institution | Kabale University |
| issn | 2058-7716 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-a5b8e3e0210e484c983f29faca411d6a2025-01-26T12:15:23ZengNature Publishing GroupCell Death Discovery2058-77162025-01-0111111010.1038/s41420-025-02293-3IDO1 inhibits ferroptosis by regulating FTO-mediated m6A methylation and SLC7A11 mRNA stability during glioblastoma progressionQianting Tian0Guixue Dan1Xuyan Wang2Jiamei Zhu3Chaochun Chen4Dekun Tang5Ziming Wang6Dan Chen7Shan Lei8Chao Yang9Houmei Wang10Bing Guo11Bangming Jin12Tengxiang Chen13Lei Tang14Department of Physiology, School of Basic Medical Sciences, Guizhou Medical UniversityDepartment of Physiology, School of Basic Medical Sciences, Guizhou Medical UniversityDepartment of Physiology, School of Basic Medical Sciences, Guizhou Medical UniversityDepartment of Physiology, School of Basic Medical Sciences, Guizhou Medical UniversityDepartment of Physiology, School of Basic Medical Sciences, Guizhou Medical UniversityDepartment of Physiology, School of Basic Medical Sciences, Guizhou Medical UniversityDepartment of Physiology, School of Basic Medical Sciences, Guizhou Medical UniversityDepartment of Physiology, School of Basic Medical Sciences, Guizhou Medical UniversityDepartment of Physiology, School of Basic Medical Sciences, Guizhou Medical UniversityState Key Laboratory of Functions and Applications of Medicinal Plants, School of Basic Medical Sciences, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical UniversityDepartment of Physiology, School of Basic Medical Sciences, Guizhou Medical UniversityDepartment of Physiology, School of Basic Medical Sciences, Guizhou Medical UniversityDepartment of Physiology, School of Basic Medical Sciences, Guizhou Medical UniversityDepartment of Physiology, School of Basic Medical Sciences, Guizhou Medical UniversityState Key Laboratory of Functions and Applications of Medicinal Plants, School of Basic Medical Sciences, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical UniversityAbstract 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.https://doi.org/10.1038/s41420-025-02293-3 |
| spellingShingle | 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 IDO1 inhibits ferroptosis by regulating FTO-mediated m6A methylation and SLC7A11 mRNA stability during glioblastoma progression Cell Death Discovery |
| title | IDO1 inhibits ferroptosis by regulating FTO-mediated m6A methylation and SLC7A11 mRNA stability during glioblastoma progression |
| title_full | IDO1 inhibits ferroptosis by regulating FTO-mediated m6A methylation and SLC7A11 mRNA stability during glioblastoma progression |
| title_fullStr | IDO1 inhibits ferroptosis by regulating FTO-mediated m6A methylation and SLC7A11 mRNA stability during glioblastoma progression |
| title_full_unstemmed | IDO1 inhibits ferroptosis by regulating FTO-mediated m6A methylation and SLC7A11 mRNA stability during glioblastoma progression |
| title_short | IDO1 inhibits ferroptosis by regulating FTO-mediated m6A methylation and SLC7A11 mRNA stability during glioblastoma progression |
| title_sort | ido1 inhibits ferroptosis by regulating fto mediated m6a methylation and slc7a11 mrna stability during glioblastoma progression |
| url | https://doi.org/10.1038/s41420-025-02293-3 |
| work_keys_str_mv | AT qiantingtian ido1inhibitsferroptosisbyregulatingftomediatedm6amethylationandslc7a11mrnastabilityduringglioblastomaprogression AT guixuedan ido1inhibitsferroptosisbyregulatingftomediatedm6amethylationandslc7a11mrnastabilityduringglioblastomaprogression AT xuyanwang ido1inhibitsferroptosisbyregulatingftomediatedm6amethylationandslc7a11mrnastabilityduringglioblastomaprogression AT jiameizhu ido1inhibitsferroptosisbyregulatingftomediatedm6amethylationandslc7a11mrnastabilityduringglioblastomaprogression AT chaochunchen ido1inhibitsferroptosisbyregulatingftomediatedm6amethylationandslc7a11mrnastabilityduringglioblastomaprogression AT dekuntang ido1inhibitsferroptosisbyregulatingftomediatedm6amethylationandslc7a11mrnastabilityduringglioblastomaprogression AT zimingwang ido1inhibitsferroptosisbyregulatingftomediatedm6amethylationandslc7a11mrnastabilityduringglioblastomaprogression AT danchen ido1inhibitsferroptosisbyregulatingftomediatedm6amethylationandslc7a11mrnastabilityduringglioblastomaprogression AT shanlei ido1inhibitsferroptosisbyregulatingftomediatedm6amethylationandslc7a11mrnastabilityduringglioblastomaprogression AT chaoyang ido1inhibitsferroptosisbyregulatingftomediatedm6amethylationandslc7a11mrnastabilityduringglioblastomaprogression AT houmeiwang ido1inhibitsferroptosisbyregulatingftomediatedm6amethylationandslc7a11mrnastabilityduringglioblastomaprogression AT bingguo ido1inhibitsferroptosisbyregulatingftomediatedm6amethylationandslc7a11mrnastabilityduringglioblastomaprogression AT bangmingjin ido1inhibitsferroptosisbyregulatingftomediatedm6amethylationandslc7a11mrnastabilityduringglioblastomaprogression AT tengxiangchen ido1inhibitsferroptosisbyregulatingftomediatedm6amethylationandslc7a11mrnastabilityduringglioblastomaprogression AT leitang ido1inhibitsferroptosisbyregulatingftomediatedm6amethylationandslc7a11mrnastabilityduringglioblastomaprogression |