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METTL3 facilitates colorectal cancer growth through altering the abundance of intestinal Akkermansia muciniphila.

Cancer gene therapy 2025 Vol.32(10) p. 1098-1106

Wu L, Lian W, Bai R, Chen H, Wu J, Li H, Zhao L

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Colorectal cancer (CRC) is a prevalent malignant tumor that poses a significant threat to human health; however, the precise mechanism underlying its onset remains elusive.

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APA Wu L, Lian W, et al. (2025). METTL3 facilitates colorectal cancer growth through altering the abundance of intestinal Akkermansia muciniphila.. Cancer gene therapy, 32(10), 1098-1106. https://doi.org/10.1038/s41417-025-00949-x
MLA Wu L, et al.. "METTL3 facilitates colorectal cancer growth through altering the abundance of intestinal Akkermansia muciniphila.." Cancer gene therapy, vol. 32, no. 10, 2025, pp. 1098-1106.
PMID 40790086

Abstract

Colorectal cancer (CRC) is a prevalent malignant tumor that poses a significant threat to human health; however, the precise mechanism underlying its onset remains elusive. In this study, we utilized metagenomic sequencing to reveal the dysregulation of intestinal microbiota caused by CRC. Single-cell sequencing data showed elevated mRNA expression of methyltransferase-like protein 3 (METTL3) in CRC, which was correlated with the abundance of intestinal microbiota. Furthermore, we found that METTL3 promotion of CRC progression is microbiota-dependent. Using induced METTL3 Vil1-cre mice, we identified the microbiota regulated by METTL3 in CRC. Our research indicates that METTL3 leads to high expression of HIF1α, which promotes the expression of lipocalin 2 (LCN2) in CRC cells, inhibiting the abundance of Akkermansia muciniphila, thereby promoting CRC progression.

MeSH Terms

Colorectal Neoplasms; Animals; Mice; Humans; Gastrointestinal Microbiome; Methyltransferases; Akkermansia; Cell Line, Tumor

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