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<p>Transposable elements (TEs) comprising nearly 50% of the genome are generally silenced by epigenetic mechanisms. Epigenetic anti-cancer drugs can lead to their re-expression, however, the role of TEs in tumorigenesis is unknown. Here, we demonstrate that TEs and their activation of a viral mimicry response plays an important tumor suppressive role in inflammation. We discovered that both patients and mice with colitis express TEs that lead to a viral mimicry response. Interestingly, this response inhibits stemness of cancer-initiating cells. Further activation of viral mimicry by DNA hypomethylation inhibits tumorigenesis. Conversely, knockout of the anti-viral signaling protein MAVS promotes tumorigenesis and reverses the anti-tumor effect of DNA hypomethylation, confirming a tumor suppressive role of viral mimicry. Consistent with this finding, patients with colitis-associated dysplasia show decreased expression of TEs and interferon-related genes. These findings suggest that activation of viral mimicry inhibits stemness and plays a key tumor suppressive role in inflammation.</p>

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Viral mimicry acts as a tumor suppressor in colitis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月4日

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  • Frederikke Larsen,
  • Will Jeong,
  • Daniel Schep,
  • Hayley J. Good,
  • Alice E. Shin,
  • Liyue Zhang,
  • Mathieu F. Derouet,
  • Timothy C. Wang,
  • Christina A. Castellani,
  • Parisa Shooshtari,
  • Samuel Asfaha

摘要

Transposable elements (TEs) comprising nearly 50% of the genome are generally silenced by epigenetic mechanisms. Epigenetic anti-cancer drugs can lead to their re-expression, however, the role of TEs in tumorigenesis is unknown. Here, we demonstrate that TEs and their activation of a viral mimicry response plays an important tumor suppressive role in inflammation. We discovered that both patients and mice with colitis express TEs that lead to a viral mimicry response. Interestingly, this response inhibits stemness of cancer-initiating cells. Further activation of viral mimicry by DNA hypomethylation inhibits tumorigenesis. Conversely, knockout of the anti-viral signaling protein MAVS promotes tumorigenesis and reverses the anti-tumor effect of DNA hypomethylation, confirming a tumor suppressive role of viral mimicry. Consistent with this finding, patients with colitis-associated dysplasia show decreased expression of TEs and interferon-related genes. These findings suggest that activation of viral mimicry inhibits stemness and plays a key tumor suppressive role in inflammation.