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NR0B1 suppresses ferroptosis through upregulation of NRF2/c-JUN-CBS signaling pathway in lung cancer cells

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机构： [1]Department of Medical Genetics and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University Chengdu 610041, Sichuan, China. [2]Department of Pathology and Infectious Diseases, People's Hospital of Deyang City Deyang 618000, Sichuan, China. [3]Institute of Gerontology and Center for Geriatrics, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China Chengdu 610071, Sichuan, China.

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关键词： NR0B1 ferroptosis CBS NRF2 c-JUN lung cancer drug resistance

摘要：

Ferroptosis has demonstrated significant potential in treating radiochemotherapy-resistant cancers, but its efficacy can be affected by recently discovered ferroptosis suppressors. In this study, we discovered that NR0B1 protects against erastin- or RSL3-induced ferroptosis in lung cancer cells. Transcriptomic analysis revealed that NR0B1 significantly interfered with the expression of 12 ferroptosis-related genes, and the expression level of NR0B1 positively correlated with that of c-JUN, NRF2, and CBS. We further revealed that NR0B1 suppression of ferroptosis depended on the activities of c-JUN, NRF2, and CBS. NR0B1 directly promoted the expression of NRF2 and c-JUN and indirectly upregulated CBS expression through enhancing NRF2 and/or c-JUN transcription. Moreover, we showed that NR0B1 depletion restrained xenograft tumor growth and facilitated RSL3-induced ferroptosis in the tumors. In conclusion, our findings uncover that NR0B1 suppresses ferroptosis by activating the c-JUN/NRF2-CBS signaling pathway in lung cancer cells, providing new evidence for the involvement of NR0B1 in drug resistance during cancer therapy.AJCR Copyright © 2023.

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出版当年[2023]版：

大类 | 3 区医学

小类 | 3 区肿瘤学

最新[2023]版：

大类 | 3 区医学

小类 | 3 区肿瘤学

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出版当年[2023]版：

Q2 ONCOLOGY

最新[2023]版：

Q2 ONCOLOGY

影响因子： 3.6 最新[2023版] 4.5 最新五年平均 3.6 出版当年[2023版] 4.5 出版当年五年平均 5.3 出版前一年[2022版]

第一作者：

第一作者机构： [1]Department of Medical Genetics and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University Chengdu 610041, Sichuan, China.

通讯作者：

通讯机构： [1]Department of Medical Genetics and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University Chengdu 610041, Sichuan, China. [*1]Department of Medical Genetics and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.

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