Wu Ling, Lian Weidong, Bai Rui, Chen Hao, Wu Jianghua, Li Hanyu, Zhao Liang
Department of Pathology, The Eighth Affiliated Hospital, Southern Medical University (The First People's Hospital of Shunde, Foshan), Foshan, China.
Department of Pathology & Guangdong Province Key Laboratory of Molecular Tumor Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
Cancer Gene Ther. 2025 Aug 11. doi: 10.1038/s41417-025-00949-x.
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.
结直肠癌（CRC）是一种常见的恶性肿瘤，对人类健康构成重大威胁；然而，其发病的确切机制仍不清楚。在本研究中，我们利用宏基因组测序揭示了CRC导致的肠道微生物群失调。单细胞测序数据显示，CRC中甲基转移酶样蛋白3（METTL3）的mRNA表达升高，这与肠道微生物群的丰度相关。此外，我们发现METTL3促进CRC进展是依赖微生物群的。使用诱导型METTL3 Vil1-cre小鼠，我们鉴定了CRC中受METTL3调节的微生物群。我们的研究表明，METTL3导致HIF1α高表达，促进CRC细胞中lipocalin 2（LCN2）的表达，抑制嗜黏蛋白阿克曼氏菌的丰度，从而促进CRC进展。
