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m6A and m5C modification of GPX4 facilitates anticancer immunity via STING activation

Baoxiang Chen1,2,3,4, Yuntian Hong1,2,3, Xiang Zhai1,2,3

  • 1Department of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.

Cell Death & Disease
|December 8, 2023
PubMed

Insights

Glutathione peroxidase 4 (GPX4) is upregulated in colon cancer, enhancing immune cell infiltration. Its modifications (m6A and m5C) activate the cGAS-STING pathway, offering a promising target for cancer immunotherapy.

Area of Science:

  • Oncology
  • Immunology
  • Biochemistry

Background:

  • Cancer immunotherapy is a rapidly evolving field.
  • Glutathione peroxidase 4 (GPX4) is crucial for preventing lipid peroxidation and maintaining cellular redox balance.
  • The role of GPX4 in colon adenocarcinoma (COAD) immunotherapy is not fully understood.

Purpose of the Study:

  • To investigate the expression and function of GPX4 in COAD.
  • To explore the mechanisms by which GPX4 influences anticancer immunity.
  • To assess the prognostic and therapeutic value of GPX4 in COAD.

Main Methods:

  • Pan-cancer analysis of GPX4 expression and its correlation with survival.
  • Analysis of GPX4's association with immune cell infiltration and immunomodulators.
  • Investigation of GPX4 modifications (m6A and m5C) and their impact on the cGAS-STING signaling pathway.

Main Results:

  • GPX4 is significantly upregulated in multiple cancers, particularly COAD, and associated with better overall survival.
  • Upregulated GPX4 correlates with increased immune cell infiltration and immunomodulator expression.
  • GPX4 modifications (m6A and m5C) activate the cGAS-STING pathway by maintaining redox homeostasis, enhancing anti-COAD immunity.

Conclusions:

  • GPX4 plays a vital role in COAD progression and immune response.
  • GPX4 modifications, specifically m6A and m5C, are key regulators of anticancer immunity via the cGAS-STING pathway.
  • Targeting GPX4 modifications presents a promising strategy for COAD immunotherapy.

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