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

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 methyltransfer...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10067857/
https://www.ncbi.nlm.nih.gov/pubmed/37005412
http://dx.doi.org/10.1038/s41419-023-05752-w
Descripción
Sumario: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.