Clostridium butyricum inhibits epithelial–mesenchymal transition of intestinal carcinogenesis through downregulating METTL3

Colorectal cancer (CRC) is related to gut microbiota dysbiosis, especially butyrate‐producing bacteria reduction. Our previous study suggested that administration of Clostridium butyricum, a butyrate‐producing bacterium, exerts a crucial effect against CRC, however the potential mechanism is not clear. We first found that methyltransferase‐like 3 (METTL3) showed a positive correlation with proliferation, epithelial–mesenchymal transition (EMT), DNA repair, metastasis, and invasion in a database analysis. The expression of METTL3 gradually increased from human normal colon tissue, to adenoma, and carcinoma, and was positively correlated with E‐cadherin and CD34 levels. Overexpression of METTL3 promoted the proliferation, migration, and invasion of CRC cells and induced vasculogenic mimicry (VM) formation. Clostridium butyricum could downregulate METTL3 expression in CRC cells and decrease the expression of vimentin and vascular endothelial growth factor receptor 2 to reduce EMT and VM formation. Clostridium butyricum alleviated the pro‐oncogenic effect of METTL3 overexpressing plasmid in CRC cells. The anti‐EMT effect on METTL3 reduction of C. butyricum could be blunted by knocking down G‐protein coupled receptor 43. Moreover, C. butyricum prevented EMT and VM and inhibited tumor metastasis in nude mice. Accordingly, C. butyricum could inhibit EMT and VM formation of intestinal carcinogenesis through downregulating METTL3. These findings broaden our understanding of probiotics supplement in CRC prevention and treatment.

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