TRIM7 modulates NCOA4-mediated ferritinophagy and ferroptosis in glioblastoma cells
Kaiqiang Li,
Bingyu Chen,
Aibo Xu,
Jinglan Shen,
Kaixuan Li,
Ke Hao,
Rongrong Hao,
Wei Yang,
Wanli Jiang,
Yongfa Zheng,
Feihang Ge,
Zhen Wang
Affiliations
Kaiqiang Li
Center for Laboratory Medicine, Allergy Center, Department of Transfusion Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China; Key Laboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang Province, Cancer Center, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China; Hangzhou Chinese Academy of Sciences-Hangzhou Medical College Advanced Medical Technology Institute, Hangzhou, 310014, China
Bingyu Chen
Center for Laboratory Medicine, Allergy Center, Department of Transfusion Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China
Aibo Xu
Key Laboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang Province, Cancer Center, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China; Hangzhou Chinese Academy of Sciences-Hangzhou Medical College Advanced Medical Technology Institute, Hangzhou, 310014, China
Jinglan Shen
Center for Laboratory Medicine, Allergy Center, Department of Transfusion Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China; Key Laboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang Province, Cancer Center, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China
Kaixuan Li
Center for Laboratory Medicine, Allergy Center, Department of Transfusion Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China; Key Laboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang Province, Cancer Center, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China; Hangzhou Chinese Academy of Sciences-Hangzhou Medical College Advanced Medical Technology Institute, Hangzhou, 310014, China
Ke Hao
Center for Laboratory Medicine, Allergy Center, Department of Transfusion Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China; Key Laboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang Province, Cancer Center, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China; Hangzhou Chinese Academy of Sciences-Hangzhou Medical College Advanced Medical Technology Institute, Hangzhou, 310014, China
Rongrong Hao
Key Laboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang Province, Cancer Center, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China; Hangzhou Chinese Academy of Sciences-Hangzhou Medical College Advanced Medical Technology Institute, Hangzhou, 310014, China
Wei Yang
Center for Laboratory Medicine, Allergy Center, Department of Transfusion Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China
Wanli Jiang
Hangzhou Chinese Academy of Sciences-Hangzhou Medical College Advanced Medical Technology Institute, Hangzhou, 310014, China; Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, China
Yongfa Zheng
Center of Oncology, Renmin Hospital of Wuhan University, Wuhan, 430060, China; Corresponding author.
Feihang Ge
Hangzhou Chinese Academy of Sciences-Hangzhou Medical College Advanced Medical Technology Institute, Hangzhou, 310014, China; Corresponding author.
Zhen Wang
Center for Laboratory Medicine, Allergy Center, Department of Transfusion Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China; Key Laboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang Province, Cancer Center, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China; Hangzhou Chinese Academy of Sciences-Hangzhou Medical College Advanced Medical Technology Institute, Hangzhou, 310014, China; Corresponding author. Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China.
Objective: Glioblastoma is one of the most common intracranial malignant tumors with an unfavorable prognosis, and iron metabolism as well as ferroptosis are implicated in the pathogenesis of glioblastoma. The present study aims to decipher the role and mechanisms of tripartite motif-containing protein 7 (TRIM7) in ferroptosis and glioblastoma progression. Methods: Stable TRIM7-deficient or overexpressing human glioblastoma cells were generated with lentiviral vectors, and cell survival, lipid peroxidation and iron metabolism were evaluated. Immunoprecipitation, protein degradation and ubiquitination assays were performed to demonstrate the regulation of TRIM7 on its candidate proteins. Results: TRIM7 expression was elevated in human glioblastoma cells and tissues. TRIM7 silence suppressed growth and induced death, while TRIM7 overexpression facilitated growth and inhibited death of human glioblastoma cells. Meanwhile, TRIM7-silenced cells exhibited increased iron accumulation, lipid peroxidation and ferroptosis, which were significantly reduced by TRIM7 overexpression. Mechanistically, TRIM7 directly bound to and ubiquitinated nuclear receptor coactivator 4 (NCOA4) using K48-linked chains, thereby reducing NCOA4-mediated ferritinophagy and ferroptosis of human glioblastoma cells. Moreover, we found that TRIM7 deletion sensitized human glioblastoma cells to temozolomide therapy. Conclusion: We for the first time demonstrate that TRIM7 modulates NCOA4-mediated ferritinophagy and ferroptosis in glioblastoma cells, and our findings provide a novel insight into the progression and treatment for human glioblastoma.
