PRMT1 reverts the immune escape of necroptotic colon cancer through RIP3 methylation.
PRMT1 reverts the immune escape of necroptotic colon cancer through RIP3 methylation.
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DOI：
10.1038/s41419-023-05752-w
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发表时间：
2023-04-01
影响因子：
9
通讯作者：
Jin, Guoxiang
中科院分区：
文献类型：
--
作者：
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
坏死性下垂在坏死性癌细胞死亡和肿瘤免疫逃逸中起着双刃剑的作用。癌症如何协调坏死性下垂与免疫逃逸和肿瘤进展在很大程度上仍不清楚。我们发现，人的RIP3R486和小鼠的保守氨基酸R479上的PRMT1甲基转移酶分别对RIP3和R479进行甲基化。PRMT1对RIP3的甲基化抑制了RIP3与RIP1的相互作用，从而抑制了RIP1-RIP3的核小体复合体，从而阻断了RIP3的磷酸化和坏死下垂的激活。此外，甲基化缺陷的RIP3突变体通过增加肿瘤浸润性髓系免疫抑制细胞(MDSC)而促进坏死性下垂、免疫逃逸和结肠癌进展，而PRMT1逆转了RIP3坏死性结肠癌的免疫逃逸。重要的是，我们产生了RIP3 R486二甲基化特异性抗体(RIP3ADMA)。临床标本分析显示，癌组织中PRMT1和RIP3ADMA的蛋白水平呈正相关，两者均预示着患者较长的生存期。我们的研究揭示了PRMT1介导的RIP3甲基化调控结肠癌免疫功能的分子机制，并揭示了PRMT1和RIP3ADMA是有价值的结肠癌预后标记物。
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 (RIP3ADMA). Clinical patient samples analysis revealed that the protein levels of PRMT1 and RIP3ADMA 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 RIP3ADMA as the valuable prognosis markers of colon cancer.
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影响因子：
5.2
作者：
Suresh S;Huard S;Brisson A;Némati F;Dakroub R;Poulard C;Ye M;Martel E;Reyes C;Silvestre DC;Meseure D;Nicolas A;Gentien D;Fayyad-Kazan H;Le Romancer M;Decaudin D;Roman-Roman S;Dubois T
通讯作者：
Dubois T
PRMT1 促进 p14(ARF) 的肿瘤抑制功能，并指示胰腺癌的预后。
DOI：
10.15252/embj.2020106777
发表时间：
2021-07-01
期刊：
The EMBO journal
影响因子：
--
作者：
Repenning A;Happel D;Bouchard C;Meixner M;Verel-Yilmaz Y;Raifer H;Holembowski L;Krause E;Kremmer E;Feederle R;Keber CU;Lohoff M;Slater EP;Bartsch DK;Bauer UM
通讯作者：
Bauer UM
影响因子：
4.6
作者：
Lin, Zhibin;Chen, Yao;Dong, Yangyang
通讯作者：
Dong, Yangyang
影响因子：
16
作者：
Choi, Seung-Won;Park, Han-Hee;Kim, You-Sun
通讯作者：
Kim, You-Sun
影响因子：
44.1
作者：
Koo, Gi-Bang;Morgan, Michael J.;Kim, You-Sun
通讯作者：
Kim, You-Sun