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Knockdown of RRM1 in tumor cells promotes radio-/chemotherapy induced ferroptosis by regulating p53 ubiquitination and p21-GPX4 signaling axis

文献类型：期刊论文

作者Gao, Yang4,5,6; Chen, Bin5,6; Wang, Ruru5,6; Xu, An5,6; Wu, Lijun2,3; Lu, Huayi1; Zhao, Guoping5,6
刊名CELL DEATH DISCOVERY
出版日期2022-08-01
卷号8
DOI10.1038/s41420-022-01140-z
通讯作者Lu, Huayi(Lhy510@jlu.edu.cn) ; Zhao, Guoping(gpz@ipp.ac.cn)
英文摘要Ferroptosis, a type of regulated cell death brought about by lipid peroxidation, has been discovered to suppress tumor growth. Here, we report that targeting RRM1 promotes ferroptosis and affects sensitivity to radiation and chemotherapeutics in cancer cells. In vitro experiments demonstrate that RRM1 increases the accumulation of cellular reactive oxygen species (ROS) and lipid peroxidation by disrupting the activity and expression of the antioxidant enzyme GPX4. Further studies reveal the downstream mechanisms of RRM1, which can regulate the deubiquitinating enzyme USP11 and ubiquitinating enzyme MDM2 to affect the ubiquitination modification of p53. Unstable p53 then inhibited the activity and expression of GPX4 by restraining the p21 protein. Furthermore, our data reveal that targeting RRM1 also increases radiation-induced DNA damage and apoptotic signaling and causes crosstalk between ferroptosis and apoptosis. On the basis of our collective findings, we propose that RRM1 is an essential negative mediator of radiosensitivity through regulating ferroptosis, which could serve as a potential target to inhibit the tumor's antioxidant system and enhance the efficiency of radio/chemotherapy.
WOS关键词RIBONUCLEOTIDE REDUCTASE ; CANCER ; RADIORESISTANCE ; SUPPRESSION ; NETWORKS ; SUBUNIT ; BIOLOGY ; DEATH
资助项目National Science Fund for Excellent Young Scholars[12122510] ; National Natural Science Foundation of China[32171240] ; National Natural Science Foundation of China[31870845] ; National Natural Science Foundation of China[11835014] ; Anhui Provincial Key RD Program[202104a07020006] ; HFIPS Director's Fund[BJPY2021B07] ; HFIPS Director's Fund[YZJJZX202014]
WOS研究方向Cell Biology
语种英语
出版者SPRINGERNATURE
WOS记录号WOS:000834811500002
资助机构National Science Fund for Excellent Young Scholars ; National Natural Science Foundation of China ; Anhui Provincial Key RD Program ; HFIPS Director's Fund
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/132209]  
专题中国科学院合肥物质科学研究院
通讯作者Lu, Huayi; Zhao, Guoping
作者单位1.Univ Sci & Technol China, Affiliated Hosp USTC 1, Div Life Sci & Med, Hefei, Anhui, Peoples R China
2.Anhui Univ, Inst Informat Technol, Informat Mat & Intelligent Sensing Lab Anhui Prov, Hefei, Anhui, Peoples R China
3.Anhui Univ, Inst Phys Sci, Informat Mat & Intelligent Sensing Lab Anhui Prov, Hefei, Anhui, Peoples R China
4.Shantou Univ, Med Coll, Guangdong Prov Key Lab Infect Dis & Mol Immunopat, Shantou, Guangdong, Peoples R China
5.Chinese Acad Sci, Hefei Inst Phys Sci, Anhui Prov Key Lab Environm Toxicol & Pollut Cont, Hefei, Anhui, Peoples R China
6.Chinese Acad Sci, Key Lab High Magnet Field & Ion Beam Phys Biol, High Magnet Field Lab, Hefei, Anhui, Peoples R China
推荐引用方式
GB/T 7714		 Gao, Yang,Chen, Bin,Wang, Ruru,et al. Knockdown of RRM1 in tumor cells promotes radio-/chemotherapy induced ferroptosis by regulating p53 ubiquitination and p21-GPX4 signaling axis[J]. CELL DEATH DISCOVERY,2022,8.
APA Gao, Yang.,Chen, Bin.,Wang, Ruru.,Xu, An.,Wu, Lijun.,...&Zhao, Guoping.(2022).Knockdown of RRM1 in tumor cells promotes radio-/chemotherapy induced ferroptosis by regulating p53 ubiquitination and p21-GPX4 signaling axis.CELL DEATH DISCOVERY,8.
MLA Gao, Yang,et al."Knockdown of RRM1 in tumor cells promotes radio-/chemotherapy induced ferroptosis by regulating p53 ubiquitination and p21-GPX4 signaling axis".CELL DEATH DISCOVERY 8(2022).

入库方式： OAI收割

来源：合肥物质科学研究院

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