Triggering endogenous Z-RNA sensing for anti-tumor therapy through ZBP1-dependent necroptosis
Summary: ZBP1 senses viral Z-RNAs to induce necroptotic cell death to restrain viral infection. ZBP1 is also thought to recognize host cell-derived Z-RNAs to regulate organ development and tissue inflammation in mice. However, it remains unknown how the host-derived Z-RNAs are formed and how these e...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112472301389X |
| _version_ | 1797448083054788608 |
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| author | Tao Yang Guodong Wang Mingxiang Zhang Xiaohu Hu Qi Li Fenglin Yun Yingying Xing Xinyang Song Haibing Zhang Guohong Hu Youcun Qian |
| author_facet | Tao Yang Guodong Wang Mingxiang Zhang Xiaohu Hu Qi Li Fenglin Yun Yingying Xing Xinyang Song Haibing Zhang Guohong Hu Youcun Qian |
| author_sort | Tao Yang |
| collection | DOAJ |
| description | Summary: ZBP1 senses viral Z-RNAs to induce necroptotic cell death to restrain viral infection. ZBP1 is also thought to recognize host cell-derived Z-RNAs to regulate organ development and tissue inflammation in mice. However, it remains unknown how the host-derived Z-RNAs are formed and how these endogenous Z-RNAs are sensed by ZBP1. Here, we report that oxidative stress strongly induces host cell endogenous Z-RNAs, and the Z-RNAs then localize to stress granules for direct sensing by ZBP1 to trigger necroptosis. Oxidative stress triggers dramatically increase Z-RNA levels in tumor cells, and the Z-RNAs then directly trigger tumor cell necroptosis through ZBP1. Localization of the induced Z-RNAs to stress granules is essential for ZBP1 sensing. Oxidative stress-induced Z-RNAs significantly promote tumor chemotherapy via ZBP1-driven necroptosis. Thus, our study identifies oxidative stress as a critical trigger for Z-RNA formation and demonstrates how Z-RNAs are directly sensed by ZBP1 to trigger anti-tumor necroptotic cell death. |
| first_indexed | 2024-03-09T14:05:14Z |
| format | Article |
| id | doaj.art-d9ce3c12964e4a4497d84d11113718a9 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-09T14:05:14Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-d9ce3c12964e4a4497d84d11113718a92023-11-30T05:06:58ZengElsevierCell Reports2211-12472023-11-014211113377Triggering endogenous Z-RNA sensing for anti-tumor therapy through ZBP1-dependent necroptosisTao Yang0Guodong Wang1Mingxiang Zhang2Xiaohu Hu3Qi Li4Fenglin Yun5Yingying Xing6Xinyang Song7Haibing Zhang8Guohong Hu9Youcun Qian10CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, ChinaCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai 200031, ChinaCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, ChinaCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, ChinaCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, ChinaCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, ChinaState Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, ChinaCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, ChinaCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, ChinaCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 200031, China; Corresponding authorSummary: ZBP1 senses viral Z-RNAs to induce necroptotic cell death to restrain viral infection. ZBP1 is also thought to recognize host cell-derived Z-RNAs to regulate organ development and tissue inflammation in mice. However, it remains unknown how the host-derived Z-RNAs are formed and how these endogenous Z-RNAs are sensed by ZBP1. Here, we report that oxidative stress strongly induces host cell endogenous Z-RNAs, and the Z-RNAs then localize to stress granules for direct sensing by ZBP1 to trigger necroptosis. Oxidative stress triggers dramatically increase Z-RNA levels in tumor cells, and the Z-RNAs then directly trigger tumor cell necroptosis through ZBP1. Localization of the induced Z-RNAs to stress granules is essential for ZBP1 sensing. Oxidative stress-induced Z-RNAs significantly promote tumor chemotherapy via ZBP1-driven necroptosis. Thus, our study identifies oxidative stress as a critical trigger for Z-RNA formation and demonstrates how Z-RNAs are directly sensed by ZBP1 to trigger anti-tumor necroptotic cell death.http://www.sciencedirect.com/science/article/pii/S221112472301389XCP: CancerCP: Cell biology |
| spellingShingle | Tao Yang Guodong Wang Mingxiang Zhang Xiaohu Hu Qi Li Fenglin Yun Yingying Xing Xinyang Song Haibing Zhang Guohong Hu Youcun Qian Triggering endogenous Z-RNA sensing for anti-tumor therapy through ZBP1-dependent necroptosis Cell Reports CP: Cancer CP: Cell biology |
| title | Triggering endogenous Z-RNA sensing for anti-tumor therapy through ZBP1-dependent necroptosis |
| title_full | Triggering endogenous Z-RNA sensing for anti-tumor therapy through ZBP1-dependent necroptosis |
| title_fullStr | Triggering endogenous Z-RNA sensing for anti-tumor therapy through ZBP1-dependent necroptosis |
| title_full_unstemmed | Triggering endogenous Z-RNA sensing for anti-tumor therapy through ZBP1-dependent necroptosis |
| title_short | Triggering endogenous Z-RNA sensing for anti-tumor therapy through ZBP1-dependent necroptosis |
| title_sort | triggering endogenous z rna sensing for anti tumor therapy through zbp1 dependent necroptosis |
| topic | CP: Cancer CP: Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S221112472301389X |
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