PRMT1 reverts the immune escape of necroptotic colon cancer through RIP3 methylation

作者全名："Zhang, Lian; He, Yujiao; Jiang, Yi; Wu, Qi; Liu, Yanchen; Xie, Qingqiang; Zou, Yuxiu; Wu, Jiaqian; Zhang, Chundong; Zhou, Zhongjun; Bian, Xiu-Wu; Jin, Guoxiang"

作者地址："[Zhang, Lian; He, Yujiao; Liu, Yanchen; Xie, Qingqiang; Zou, Yuxiu; Jin, Guoxiang] Southern Med Univ, Guangdong Prov Peoples Hosp, Med Res Inst, Guangdong Cardiovasc Inst,Guangdong Acad Med Sci, Guangzhou 510080, Peoples R China; [Zhang, Lian; Jiang, Yi; Wu, Qi; Wu, Jiaqian; Bian, Xiu-Wu; Jin, Guoxiang] Third Mil Med Univ, Army Med Univ, Inst Pathol, Chongqing 400038, Peoples R China; [Zhang, Lian; Jiang, Yi; Wu, Jiaqian; Bian, Xiu-Wu; Jin, Guoxiang] Third Mil Med Univ, Army Med Univ, Southwest Hosp, Southwest Canc Ctr, Chongqing, Peoples R China; [Zhang, Lian; Jiang, Yi; Wu, Jiaqian; Bian, Xiu-Wu; Jin, Guoxiang] Minist Educ China, Key Lab Tumor Immunopathol, Chongqing 400038, Peoples R China; [Zhang, Lian; Zhou, Zhongjun] Univ Hong Kong, LKS Fac Med, Sch Biomed Sci, Hong Kong, Peoples R China; [Zhang, Lian] Chongqing Med Univ, Coll Basic Med Sci, Chongqing 400016, Peoples R China; [Zhang, Chundong] Chongqing Med Univ, Coll Basic Med Sci, Dept Biochem & Mol Biol, Chongqing 400016, Peoples R China"

通信作者："Jin, GX (通讯作者)，Southern Med Univ, Guangdong Prov Peoples Hosp, Med Res Inst, Guangdong Cardiovasc Inst,Guangdong Acad Med Sci, Guangzhou 510080, Peoples R China.; Bian, XW; Jin, GX (通讯作者)，Third Mil Med Univ, Army Med Univ, Inst Pathol, Chongqing 400038, Peoples R China.; Bian, XW; Jin, GX (通讯作者)，Third Mil Med Univ, Army Med Univ, Southwest Hosp, Southwest Canc Ctr, Chongqing, Peoples R China.; Bian, XW; Jin, GX (通讯作者)，Minist Educ China, Key Lab Tumor Immunopathol, Chongqing 400038, Peoples R China.; Zhou, ZJ (通讯作者)，Univ Hong Kong, LKS Fac Med, Sch Biomed Sci, Hong Kong, Peoples R China."

来源：CELL DEATH & DISEASE

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000961419800001

JCR分区：Q1

影响因子：9

年份：2023

卷号：14

期号：4

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Necroptosis plays a double-edged sword role in necroptotic cancer cell death and tumor immune escape. How cancer orchestrates necroptosis with immune escape and tumor progression remains largely unclear. We found that RIP3, the central activator of necroptosis, was methylated by PRMT1 methyltransferase at the amino acid of RIP3 R486 in human and the conserved amino acid R479 in mouse. The methylation of RIP3 by PRMT1 inhibited the interaction of RIP3 with RIP1 to suppress RIP1-RIP3 necrosome complex, thereby blocking RIP3 phosphorylation and necroptosis activation. Moreover, the methylation-deficiency RIP3 mutant promoted necroptosis, immune escape and colon cancer progression due to increasing tumor infiltrated myeloid-derived immune suppressor cells (MDSC), while PRMT1 reverted the immune escape of RIP3 necroptotic colon cancer. Importantly, we generated a RIP3 R486 di-methylation specific antibody (RIP3(ADMA)). Clinical patient samples analysis revealed that the protein levels of PRMT1 and RIP3(ADMA) were positively correlated in cancer tissues and both of them predicted the longer patient survival. Our study provides insights into the molecular mechanism of PRMT1-mediated RIP3 methylation in the regulation of necroptosis and colon cancer immunity, as well as reveals PRMT1 and RIP3(ADMA) as the valuable prognosis markers of colon cancer."

基金机构："National Natural Science Foundation of China [82273180, 81972774, 81821003]; Science and Technology Innovation Project of Chongqing Science and Technology Commission [cstc2018jcyj-yszxX0011]; Guangdong Provincial People's Hospital, High-level Hospital Construction Project [KJ012021074, KJ012019517]"

基金资助正文："AcknowledgementsWe thank all lab members for their valuable reading, comments and suggestions. The study was supported by grants from National Natural Science Foundation of China (82273180, 81972774 to GJ and 81821003 to XWB), Science and Technology Innovation Project of Chongqing Science and Technology Commission (cstc2018jcyj-yszxX0011) and Guangdong Provincial People's Hospital, High-level Hospital Construction Project (KJ012021074, KJ012019517)."