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

IF 5 3区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Cancer gene therapy Pub Date : 2025-08-11 DOI:10.1038/s41417-025-00949-x

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

引用次数: 0

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 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.

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METTL3通过改变肠道嗜黏液阿克曼氏菌的丰度促进结直肠癌的生长。

结直肠癌（CRC）是一种普遍存在的恶性肿瘤，对人类健康构成重大威胁；然而，其发病的确切机制仍然难以捉摸。在这项研究中，我们利用宏基因组测序来揭示CRC引起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) mRNA表达升高，这与肠道菌群丰度相关。此外，我们发现METTL3促进CRC进展是依赖于微生物群的。使用诱导的METTL3 /fl Vil1-cre+/-小鼠，我们确定了METTL3在CRC中调节的微生物群。我们的研究表明，METTL3导致HIF1α高表达，从而促进CRC细胞中脂载蛋白2 （lipocalin 2, LCN2）的表达，抑制嗜粘Akkermansia muciniinia的丰度，从而促进CRC的进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer gene therapy 医学-生物工程与应用微生物

CiteScore

10.20

自引率

0.00%

发文量

150

审稿时长

4-8 weeks

期刊介绍： Cancer Gene Therapy is the essential gene and cellular therapy resource for cancer researchers and clinicians, keeping readers up to date with the latest developments in gene and cellular therapies for cancer. The journal publishes original laboratory and clinical research papers, case reports and review articles. Publication topics include RNAi approaches, drug resistance, hematopoietic progenitor cell gene transfer, cancer stem cells, cellular therapies, homologous recombination, ribozyme technology, antisense technology, tumor immunotherapy and tumor suppressors, translational research, cancer therapy, gene delivery systems (viral and non-viral), anti-gene therapy (antisense, siRNA & ribozymes), apoptosis; mechanisms and therapies, vaccine development, immunology and immunotherapy, DNA synthesis and repair. Cancer Gene Therapy publishes the results of laboratory investigations, preclinical studies, and clinical trials in the field of gene transfer/gene therapy and cellular therapies as applied to cancer research. Types of articles published include original research articles; case reports; brief communications; review articles in the main fields of drug resistance/sensitivity, gene therapy, cellular therapy, tumor suppressor and anti-oncogene therapy, cytokine/tumor immunotherapy, etc.; industry perspectives; and letters to the editor.