Tian Qianting, Dan Guixue, Wang Xuyan, Zhu Jiamei, Chen Chaochun, Tang Dekun, Wang Ziming, Chen Dan, Lei Shan, Yang Chao, Wang Houmei, Guo Bing, Jin Bangming, Chen Tengxiang, Tang Lei
Department of Physiology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, China.
Transformation Engineering Research Center of Chronic Disease Diagnosis and Treatment, Guizhou Medical University, Guiyang, China.
Cell Death Discov. 2025 Jan 25;11(1):22. doi: 10.1038/s41420-025-02293-3.
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.
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且具有免疫抑制能力的酶。本研究旨在探讨IDO1对多形性胶质母细胞瘤（GBM）细胞的影响。在此，我们发现IDO1在胶质瘤患者中表达显著增加，并与GBM进展相关。IDO1过表达抑制了GBM细胞的铁死亡，减少了活性氧（ROS）和脂质过氧化物的产生。IDO1表达通过FTO依赖的m6A甲基化增加了溶质载体家族7成员11（SLC7A11）mRNA的稳定性。机制上，IDO1促进芳烃受体（AhR）的表达和核转位，从而促进AhR在FTO基因启动子区域的募集并负向调节其转录。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依赖性铁死亡，从而促进GBM进展。
