Helicobacter pylori reduces METTL14-mediated VAMP3 m6A modification and promotes the development of gastric cancer by regulating LC3C-mediated c-Met recycling
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 th...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-01-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-025-02289-z |
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| author | Xixi Cui Mingjie Chang Yuqiong Wang Jiayi Liu Zenghui Sun Qiyu Sun Yundong Sun Juchao Ren Wenjuan Li |
| author_facet | Xixi Cui Mingjie Chang Yuqiong Wang Jiayi Liu Zenghui Sun Qiyu Sun Yundong Sun Juchao Ren Wenjuan Li |
| author_sort | Xixi Cui |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-655ca9cbf5a142e09b5f0a5c82f4c12a |
| institution | Kabale University |
| issn | 2058-7716 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-655ca9cbf5a142e09b5f0a5c82f4c12a2025-01-19T12:10:33ZengNature Publishing GroupCell Death Discovery2058-77162025-01-0111111310.1038/s41420-025-02289-zHelicobacter pylori reduces METTL14-mediated VAMP3 m6A modification and promotes the development of gastric cancer by regulating LC3C-mediated c-Met recyclingXixi Cui0Mingjie Chang1Yuqiong Wang2Jiayi Liu3Zenghui Sun4Qiyu Sun5Yundong Sun6Juchao Ren7Wenjuan Li8Key Laboratory for Experimental Teratology of Chinese Ministry of Education, The Shandong Provincial Key Laboratory of Infection and Immunology, Department of Pathogenic biology, School of basic medical sciences, Cheeloo College of Medicine, Shandong UniversityKey Laboratory for Experimental Teratology of Chinese Ministry of Education, The Shandong Provincial Key Laboratory of Infection and Immunology, Department of Pathogenic biology, School of basic medical sciences, Cheeloo College of Medicine, Shandong UniversityKey Laboratory for Experimental Teratology of Chinese Ministry of Education, The Shandong Provincial Key Laboratory of Infection and Immunology, Department of Pathogenic biology, School of basic medical sciences, Cheeloo College of Medicine, Shandong UniversityKey Laboratory for Experimental Teratology of Chinese Ministry of Education, The Shandong Provincial Key Laboratory of Infection and Immunology, Department of Pathogenic biology, School of basic medical sciences, Cheeloo College of Medicine, Shandong UniversityKey Laboratory for Experimental Teratology of Chinese Ministry of Education, The Shandong Provincial Key Laboratory of Infection and Immunology, Department of Pathogenic biology, School of basic medical sciences, Cheeloo College of Medicine, Shandong UniversityKey Laboratory for Experimental Teratology of Chinese Ministry of Education, The Shandong Provincial Key Laboratory of Infection and Immunology, Department of Pathogenic biology, School of basic medical sciences, Cheeloo College of Medicine, Shandong UniversityKey Laboratory for Experimental Teratology of Chinese Ministry of Education, The Shandong Provincial Key Laboratory of Infection and Immunology, Department of Pathogenic biology, School of basic medical sciences, Cheeloo College of Medicine, Shandong UniversityDepartment of Urology, Qilu Hospital, Shandong UniversityKey Laboratory for Experimental Teratology of Chinese Ministry of Education, The Shandong Provincial Key Laboratory of Infection and Immunology, Department of Pathogenic biology, School of basic medical sciences, Cheeloo College of Medicine, Shandong UniversityAbstract 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.https://doi.org/10.1038/s41420-025-02289-z |
| spellingShingle | Xixi Cui Mingjie Chang Yuqiong Wang Jiayi Liu Zenghui Sun Qiyu Sun Yundong Sun Juchao Ren Wenjuan Li Helicobacter pylori reduces METTL14-mediated VAMP3 m6A modification and promotes the development of gastric cancer by regulating LC3C-mediated c-Met recycling Cell Death Discovery |
| title | Helicobacter pylori reduces METTL14-mediated VAMP3 m6A modification and promotes the development of gastric cancer by regulating LC3C-mediated c-Met recycling |
| title_full | Helicobacter pylori reduces METTL14-mediated VAMP3 m6A modification and promotes the development of gastric cancer by regulating LC3C-mediated c-Met recycling |
| title_fullStr | Helicobacter pylori reduces METTL14-mediated VAMP3 m6A modification and promotes the development of gastric cancer by regulating LC3C-mediated c-Met recycling |
| title_full_unstemmed | Helicobacter pylori reduces METTL14-mediated VAMP3 m6A modification and promotes the development of gastric cancer by regulating LC3C-mediated c-Met recycling |
| title_short | Helicobacter pylori reduces METTL14-mediated VAMP3 m6A modification and promotes the development of gastric cancer by regulating LC3C-mediated c-Met recycling |
| title_sort | helicobacter pylori reduces mettl14 mediated vamp3 m6a modification and promotes the development of gastric cancer by regulating lc3c mediated c met recycling |
| url | https://doi.org/10.1038/s41420-025-02289-z |
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