| Literature DB >> 35273176 |
Shujie Chen1,2,3,4, Lu Zhang1,3,4, Mengjie Li1,3,4, Ying Zhang1,2,3,4, Meng Sun1,3,4, Lingfang Wang5, Jiebo Lin5, Yun Cui1,3,4, Qian Chen1,3,4, Chenqi Jin1,3,4, Xiang Li1,3,4, Boya Wang3,6, Hao Chen7, Tianhua Zhou8,9,10, Liangjing Wang11,12,13, Chih-Hung Hsu14, Wei Zhuo15,16,17.
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-dependent mRNA degradation, which contributes to F. nucleatum-induced CRC metastasis. Moreover, METTL3 expression is negatively correlated with F. nucleatum and KIF26B levels in CRC tissues. A high expression of KIF26B is also significantly correlated with a shorter survival time of CRC patients. Together, our findings provide insights into modulating human m6A epitranscriptome by gut microbiota, and its significance in CRC progression.Entities:
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Year: 2022 PMID： 35273176 PMCID： PMC8913623 DOI： 10.1038/s41467-022-28913-5
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919