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<p>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 (<i>METTL3</i>) 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<sup>fl/fl</sup> Vil1-cre<sup>+/−</sup> 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 <i>Akkermansia muciniphila</i>, thereby promoting CRC progression.</p>

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

  • 期刊论文

  • 发表日期：

    2025年8月11日

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  • Ling Wu,
  • Weidong Lian,
  • Rui Bai,
  • Hao Chen,
  • Jianghua Wu,
  • Hanyu Li,
  • Liang Zhao

摘要

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 METTL3fl/fl 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.