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

doi:10.1038/s41420-022-01140-z

HFCAS OpenIR

	Knockdown of RRM1 in tumor cells promotes radio-/chemotherapy induced ferroptosis by regulating p53 ubiquitination and p21-GPX4 signaling axis
	Gao, Yang 1,2,3; Chen, Bin 1,2; Wang, Ruru 1,2; Xu, An1,2 ; Wu, Lijun4,5 ; Lu, Huayi 6; Zhao, Guoping1,2
	2022-08-01
发表期刊	CELL DEATH DISCOVERY
通讯作者	Lu, Huayi(Lhy510@jlu.edu.cn) ; Zhao, Guoping(gpz@ipp.ac.cn)
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.
DOI	10.1038/s41420-022-01140-z
关键词[WOS]	RIBONUCLEOTIDE REDUCTASE ; CANCER ; RADIORESISTANCE ; SUPPRESSION ; NETWORKS ; SUBUNIT ; BIOLOGY ; DEATH
收录类别	SCI
语种	英语
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]
项目资助者	National Science Fund for Excellent Young Scholars ; National Natural Science Foundation of China ; Anhui Provincial Key RD Program ; HFIPS Director's Fund
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000834811500002
出版者	SPRINGERNATURE
引用统计	被引频次：13[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.hfcas.ac.cn:8080/handle/334002/132210
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.Chinese Acad Sci, Key Lab High Magnet Field & Ion Beam Phys Biol, High Magnet Field Lab, Hefei, Anhui, Peoples R China 2.Chinese Acad Sci, Hefei Inst Phys Sci, Anhui Prov Key Lab Environm Toxicol & Pollut Cont, Hefei, Anhui, Peoples R China 3.Shantou Univ, Med Coll, Guangdong Prov Key Lab Infect Dis & Mol Immunopat, Shantou, Guangdong, Peoples R China 4.Anhui Univ, Inst Phys Sci, Informat Mat & Intelligent Sensing Lab Anhui Prov, Hefei, Anhui, Peoples R China 5.Anhui Univ, Inst Informat Technol, Informat Mat & Intelligent Sensing Lab Anhui Prov, Hefei, Anhui, Peoples R China 6.Univ Sci & Technol China, Affiliated Hosp USTC 1, Div Life Sci & Med, 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).