Scholarlink

<p>Cyclic GMP-AMP (cGAMP) serves as a pivotal second messenger in the cGAS‒STING innate immune signaling pathway and plays a critical role in antiviral and antitumor immunity; however, its regulatory mechanisms governing the epitranscriptome remain to be elucidated. In this study, m<sup>6</sup>A methylation sequencing revealed that cGAMP induces dynamic changes in m<sup>6</sup>A modification in L929 and B16F10 cells. Mechanistic investigations revealed that cGAMP treatment significantly downregulated the expression of the RNA demethylase FTO. Although FTO deficiency suppresses cGAMP-induced interferon-stimulated gene (ISG) expression and IFN-β secretion, FTO may act as a critical node bridging cGAMP signaling and the interferon response. Further analysis revealed that the dynamic m⁶A regulation of ISGs, such as <i>DDX58</i>, is closely associated with the prognosis of tumor patients and immune cell infiltration. In vivo experiments confirmed that the targeted inhibition of FTO in combination with cGAMP exerts a synergistic antitumor effect, significantly suppressing tumor growth and prolonging survival. Overall, this study reveals the core mechanism of the "cGAMP-FTO-m⁶A" axis in innate immunity and tumor progression. These findings provide a theoretical foundation for the development of novel immunotherapies targeting the epitranscriptome.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

cGAMP suppresses FTO expression to promote m6A modification and potentiate antitumor immunity

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月25日

查看全文
  • Pan Feng,
  • Xiaolan Chen,
  • Dong Guo,
  • Zhihua Feng,
  • Yajuan Fu,
  • Junzhong Lai,
  • Xiaoyu Yang

摘要

Cyclic GMP-AMP (cGAMP) serves as a pivotal second messenger in the cGAS‒STING innate immune signaling pathway and plays a critical role in antiviral and antitumor immunity; however, its regulatory mechanisms governing the epitranscriptome remain to be elucidated. In this study, m6A methylation sequencing revealed that cGAMP induces dynamic changes in m6A modification in L929 and B16F10 cells. Mechanistic investigations revealed that cGAMP treatment significantly downregulated the expression of the RNA demethylase FTO. Although FTO deficiency suppresses cGAMP-induced interferon-stimulated gene (ISG) expression and IFN-β secretion, FTO may act as a critical node bridging cGAMP signaling and the interferon response. Further analysis revealed that the dynamic m⁶A regulation of ISGs, such as DDX58, is closely associated with the prognosis of tumor patients and immune cell infiltration. In vivo experiments confirmed that the targeted inhibition of FTO in combination with cGAMP exerts a synergistic antitumor effect, significantly suppressing tumor growth and prolonging survival. Overall, this study reveals the core mechanism of the "cGAMP-FTO-m⁶A" axis in innate immunity and tumor progression. These findings provide a theoretical foundation for the development of novel immunotherapies targeting the epitranscriptome.