IRP1 mediated ferroptosis reverses temozolomide resistance in glioblastoma via affecting LCN2/FPN1 signaling axis depended on NFKB2

Yufei Lan; Tao Yang; Qu Yue; Zhao Wang; Xiangyang Zhong; Xin Luo; Boming Zuo; Manqing Zhang; Tianci Zeng; Boyang Liu; Hongbo Guo

doi:10.1016/j.isci.2023.107377

IRP1 mediated ferroptosis reverses temozolomide resistance in glioblastoma via affecting LCN2/FPN1 signaling axis depended on NFKB2

iScience. 2023 Jul 12;26(8):107377. doi: 10.1016/j.isci.2023.107377. eCollection 2023 Aug 18.

Authors

Yufei Lan¹, Tao Yang¹, Qu Yue¹, Zhao Wang¹, Xiangyang Zhong¹, Xin Luo¹, Boming Zuo¹, Manqing Zhang¹, Tianci Zeng¹, Boyang Liu¹, Hongbo Guo¹

Affiliation

¹ Department of Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.

Abstract

The prognosis of glioblastoma (GBM) patients is poor, and temozolomide (TMZ) resistance has become an important obstacle to its treatment effect. A growing number of researches have revealed the special characteristics of iron metabolism in GBM chemosensitivity. Iron regulatory protein 1 (IRP1) is an important protein for maintaining intracellular iron homeostasis. IRP1 has been indicated to have additional vital roles beyond its conventional metabolic activity, but the underlying mechanisms and biological consequences remain elusive. Here, we unprecedentedly demonstrated that amplifying IRP1 signals can reverse TMZ resistance and suppress tumor growth in vivo via inhibiting NFKB2 in the noncanonical NF-κB signaling pathway. In addition, we identified that NFKB2 affected TMZ sensitivity of GBM by modulating the expression of LCN2 and FPN1. Taken together, this study established a role for the IRP1/NFKB2 pathway in regulating LCN2/FPN1 signaling axis among the progression of TMZ resistance, suggesting a potential innovative GBM therapeutic strategy.

Keywords: Biological sciences; Molecular biology; Oncology.