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

Lian Zhang1,2,3,4, Yujiao He1, Yi Jiang2

  • 1Medical Research Institute, Guangdong Cardiovascular Institute, Guangdong Geriatrics Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.

Cell Death & Disease
|April 3, 2023
PubMed

Insights

PRMT1 methylates RIP3, inhibiting necroptosis and promoting colon cancer immune escape. This methylation, identified by a RIP3ADMA antibody, serves as a valuable prognostic marker for longer patient survival.

Area of Science:

  • Molecular Biology
  • Immunology
  • Oncology

Background:

  • Necroptosis, a form of programmed cell death, has a complex role in cancer, influencing both cell death and immune evasion.
  • The precise mechanisms by which cancer cells manipulate necroptosis for immune escape and tumor progression are not fully understood.

Purpose of the Study:

  • To elucidate the role of RIP3 methylation by PRMT1 in regulating necroptosis, immune escape, and colon cancer progression.
  • To identify potential prognostic biomarkers for colon cancer.

Main Methods:

  • Investigated the interaction between PRMT1 methyltransferase and RIP3.
  • Utilized a methylation-deficient RIP3 mutant to study its effects on necroptosis and immune cells.
  • Developed a specific antibody (RIP3ADMA) to detect RIP3 di-methylation at R486.
  • Analyzed clinical patient samples to correlate PRMT1 and RIP3ADMA levels with patient survival.

Main Results:

  • PRMT1 methylates RIP3 at R486 (human) / R479 (mouse), inhibiting RIP1-RIP3 necrosome formation and necroptosis activation.
  • Methylation-deficiency RIP3 mutant enhanced necroptosis, immune escape, and colon cancer progression by increasing myeloid-derived suppressor cells (MDSC).
  • PRMT1 reversed immune escape in RIP3 necroptotic colon cancer.
  • High levels of PRMT1 and RIP3ADMA in patient tissues correlated positively and predicted longer survival.

Conclusions:

  • PRMT1-mediated RIP3 methylation is a key regulator of necroptosis and colon cancer immunity.
  • PRMT1 and the RIP3ADMA antibody are promising prognostic biomarkers for colon cancer.

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