Orexin-A mediates glioblastoma proliferation inhibition by increasing ferroptosis triggered by unstable iron pools and GPX4 depletion

作者全名：Huan, Rengzheng; Zhang, Jiqin; Yue, Jianhe; Yang, Sha; Han, Guoqiang; Cheng, Yuan; Tan, Ying

作者地址：[Huan, Rengzheng; Yue, Jianhe; Cheng, Yuan] Chongqing Med Univ, Affiliated Hosp 2, Dept Neurosurg, 76 Linjiang Rd, Chongqing, Peoples R China; [Zhang, Jiqin] Guizhou Prov Peoples Hosp, Dept Anesthesiol, Guiyang, Peoples R China; [Yang, Sha] Guizhou Univ, Med Coll, Dept Biomed Sci, Guiyang, Peoples R China; [Han, Guoqiang; Tan, Ying] Guizhou Prov Peoples Hosp, Dept Neurosurg, Guiyang, Peoples R China

通信作者：Cheng, Y (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Neurosurg, 76 Linjiang Rd, Chongqing, Peoples R China.; Tan, Y (通讯作者)，Guizhou Prov Peoples Hosp, Dept Neurosurg, Guiyang, Peoples R China.

来源：JOURNAL OF CELLULAR AND MOLECULAR MEDICINE

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001209487700001

JCR分区：Q2

影响因子：4.3

年份：2024

卷号：28

期号：9

开始页：　

结束页：　

文献类型：Article

关键词：ferroptosis; glioblastoma; orexin-A

摘要：Glioblastoma (GBM) represents a prevalent form of primary malignant tumours in the central nervous system, but the options for effective treatment are extremely limited. Ferroptosis, as the most enriched programmed cell death process in glioma, makes a critical difference in glioma progression. Consequently, inducing ferroptosis has become an appealing strategy for tackling gliomas. Through the utilization of multi-omics sequencing data analysis, flow cytometry, MDA detection and transmission electron microscopy, the impact of orexin-A on ferroptosis in GBM was assessed. In this report, we provide the first evidence that orexin-A exerts inhibitory effects on GBM proliferation via the induction of ferroptosis. This induction is achieved by instigating an unsustainable increase in iron levels and depletion of GPX4. Moreover, the regulation of TFRC, FTH1 and GPX4 expression through the targeting of NFE2L2 appears to be one of the potential mechanisms underlying orexin-A-induced ferroptosis.

基金机构：Guizhou Provincial Science and Technology Projects; National Natural Science Foundation of China [82360482, 82260533, 82360376]; [[2020]1Z066]

基金资助正文：The study was financially supported by the National Natural Science Foundation of China (82360482, 82260533 and 82360376) and Guizhou Provincial Science and Technology Projects ([2020]1Z066).