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 m⁶A modifications in CRC cells and patient-derived xenograft (PDX) tissues by downregulation of an m⁶A 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) expression by reducing its m⁶A levels and diminishing YTHDF2-dependen

SUBMITTER: Chen S 

PROVIDER: S-EPMC8913623 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature