Fusobacterium nucleatum reduces METTL3-mediated m6A modification and contributes to colorectal cancer metastasis

Abstract Microbiota-host interactions play critical roles in colorectal cancer (CRC) progression, however, the underlying mechanisms remain elusive. Here, we uncover that Fusobacterium nucleatum ( F. nucleatum ) induces a dramatic decline of m 6 A modifications in CRC cells and patient-derived xenograft (PDX) tissues by downregulation of an m 6 A methyltransferase METTL3, contributing to inducation of CRC aggressiveness. Mechanistically, we characterized forkhead box D3 (FOXD3) as a transcription factor for METTL3. F. nucleatum activates YAP signaling, inhibits FOXD3 expression, and subsequently reduces METTL3 transcription. Downregulation of METTL3 promotes its target kinesin family member 26B (KIF26B)…

• NN
  National Natural Science Foundation of China

  Awards: 82072623, 81972276, 31771540, 82173040, 91740205, 31972883