Helicobacter pylori reduces METTL14-mediated VAMP3 m⁶A modification and promotes the development of gastric cancer by regulating LC3C-mediated c-Met recycling.

IF 6.1 2区生物学 Q1 CELL BIOLOGY

Cell Death Discovery Pub Date : 2025-01-18 DOI:10.1038/s41420-025-02289-z

Xixi Cui, Mingjie Chang, Yuqiong Wang, Jiayi Liu, Zenghui Sun, Qiyu Sun, Yundong Sun, Juchao Ren, Wenjuan Li

{"title":"Helicobacter pylori reduces METTL14-mediated VAMP3 m6A modification and promotes the development of gastric cancer by regulating LC3C-mediated c-Met recycling.","authors":"Xixi Cui, Mingjie Chang, Yuqiong Wang, Jiayi Liu, Zenghui Sun, Qiyu Sun, Yundong Sun, Juchao Ren, Wenjuan Li","doi":"10.1038/s41420-025-02289-z","DOIUrl":null,"url":null,"abstract":"Helicobacter pylori (H. pylori) plays an important role in the malignant transformation of the gastric mucosa from chronic inflammation to cancer. However, the mechanisms underlying the epigenetic regulation of gastric carcinogenesis mediated by H. pylori remain unclear. Here, we uncover that H. pylori inhibits METTL14 by upregulating ATF3. METTL14 inhibits gastric cancer (GC) cell proliferation and metastasis in vitro and in vivo. Downregulation of METTL14 inhibits Vesicle-associated membrane protein-3 (VAMP3) by reducing the m6A modification level of VAMP3 mRNA and the stability of IGF2BP2-dependent mRNA. H. pylori also accelerates the malignant progression of GC by regulating VAMP3/LC3C-mediated c-Met recycling. Moreover, the expression of METTL14 and VAMP3 in Hp+ chronic gastritis tissues is much lower than that in Hp- chronic gastritis tissues. METTL14 and VAMP3 expression levels are downregulated notably in cancerous tissues of patients with GC. Therefore, our results show a novel METTL14-VAMP3-LC3C-c-Met signalling axis in the GC development mediated by H. pylori infection, which reveals a novel m6A epigenetic modification mechanism for GC and provides potential prognostic biomarkers for GC progression.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"13"},"PeriodicalIF":6.1000,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742886/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Death Discovery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41420-025-02289-z","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Helicobacter pylori (H. pylori) plays an important role in the malignant transformation of the gastric mucosa from chronic inflammation to cancer. However, the mechanisms underlying the epigenetic regulation of gastric carcinogenesis mediated by H. pylori remain unclear. Here, we uncover that H. pylori inhibits METTL14 by upregulating ATF3. METTL14 inhibits gastric cancer (GC) cell proliferation and metastasis in vitro and in vivo. Downregulation of METTL14 inhibits Vesicle-associated membrane protein-3 (VAMP3) by reducing the m⁶A modification level of VAMP3 mRNA and the stability of IGF2BP2-dependent mRNA. H. pylori also accelerates the malignant progression of GC by regulating VAMP3/LC3C-mediated c-Met recycling. Moreover, the expression of METTL14 and VAMP3 in Hp+ chronic gastritis tissues is much lower than that in Hp- chronic gastritis tissues. METTL14 and VAMP3 expression levels are downregulated notably in cancerous tissues of patients with GC. Therefore, our results show a novel METTL14-VAMP3-LC3C-c-Met signalling axis in the GC development mediated by H. pylori infection, which reveals a novel m⁶A epigenetic modification mechanism for GC and provides potential prognostic biomarkers for GC progression.

查看原文本刊更多论文

幽门螺杆菌通过调节lc3c介导的c-Met再循环，降低mettl14介导的VAMP3 m6A修饰，促进胃癌的发生发展。

幽门螺杆菌（Helicobacter pylori， H. pylori）在胃黏膜由慢性炎症向癌变的过程中起重要作用。然而，幽门螺杆菌介导的胃癌发生的表观遗传调控机制尚不清楚。在这里，我们发现幽门螺杆菌通过上调ATF3抑制METTL14。METTL14在体外和体内抑制胃癌细胞增殖和转移。METTL14的下调通过降低VAMP3 mRNA的m6A修饰水平和igf2bp2依赖性mRNA的稳定性来抑制Vesicle-associated membrane protein-3 （VAMP3）。幽门螺杆菌也通过调节VAMP3/ lc3c介导的c-Met循环来加速GC的恶性进展。此外，METTL14和VAMP3在Hp+慢性胃炎组织中的表达远低于Hp-慢性胃炎组织。胃癌患者癌组织中METTL14和VAMP3表达水平明显下调。因此，我们的研究结果表明，在幽门螺杆菌感染介导的GC发育中存在一种新的METTL14-VAMP3-LC3C-c-Met信号轴，这揭示了一种新的m6A表观遗传修饰机制，并为GC进展提供了潜在的预后生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

8.30

自引率

1.40%

发文量

468

审稿时长

9 weeks

期刊介绍： Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary. Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.