METTL1-mediated m7G tRNA modification drives papillary thyroid cancer progression and metastasis by regulating the codon-specific translation of TNF-α
Abstract N7-methylguanosine (m7G) modification of transfer RNA (tRNA) is essential for the biological functions of tRNAs and has been found to play a regulatory role in a variety of human cancers. However, the biological function of METTL1-mediated m7G tRNA modification in papillary thyroid cancer (...
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| Format: | Article |
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Nature Publishing Group
2025-05-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07716-8 |
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| author | Weiwei Li Ruiwang Xie Huaying Chen Junyu Lin Minjie Zhong Junsi Zhang Shengkai Zheng Cen Jiang Xiangjin Chen Sunwang Xu |
| author_facet | Weiwei Li Ruiwang Xie Huaying Chen Junyu Lin Minjie Zhong Junsi Zhang Shengkai Zheng Cen Jiang Xiangjin Chen Sunwang Xu |
| author_sort | Weiwei Li |
| collection | DOAJ |
| description | Abstract N7-methylguanosine (m7G) modification of transfer RNA (tRNA) is essential for the biological functions of tRNAs and has been found to play a regulatory role in a variety of human cancers. However, the biological function of METTL1-mediated m7G tRNA modification in papillary thyroid cancer (PTC) is unclear. Here, we found that METTL1 is significantly upregulated in PTC tissues compared to normal control tissues and is associated with poor PTC prognosis. Functional analysis confirmed that METTL1 promotes the proliferation and metastasis of PTC cells in a manner dependent on its tRNA methyltransferase activity. Mechanistically, METTL1 knockdown leads to a decrease in the abundance of certain m7G-modified tRNAs, which suppresses the m7G tRNA modification-mediated codon-specific translation of TNF-α. Furthermore, exogenous supplementation with TNF-α partially reversed the decrease in the proliferation and metastasis of PTC cells induced by METTL1 deletion. Positive correlations between METTL1, WDR4, and TNF-α expression, which affect the proliferation and metastasis of PTC, were confirmed via analysis of microarrays containing PTC tissues. These results demonstrate the oncogenic role of METTL1-mediated m7G tRNA modification in regulating codon-specific translation efficiency in PTC and suggest that targeting METTL1 may be a promising therapeutic approach for overcoming PTC progression by inhibiting PTC cell proliferation and metastasis. |
| format | Article |
| id | doaj-art-5d746f533e4b44b9a883a875392a0a13 |
| institution | OA Journals |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Publishing Group |
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| series | Cell Death and Disease |
| spelling | doaj-art-5d746f533e4b44b9a883a875392a0a132025-08-20T01:51:39ZengNature Publishing GroupCell Death and Disease2041-48892025-05-0116111410.1038/s41419-025-07716-8METTL1-mediated m7G tRNA modification drives papillary thyroid cancer progression and metastasis by regulating the codon-specific translation of TNF-αWeiwei Li0Ruiwang Xie1Huaying Chen2Junyu Lin3Minjie Zhong4Junsi Zhang5Shengkai Zheng6Cen Jiang7Xiangjin Chen8Sunwang Xu9Department of Thyroid and Breast Surgery, The First Affiliated Hospital, Fujian Medical UniversityDepartment of Thyroid and Breast Surgery, The First Affiliated Hospital, Fujian Medical UniversityDepartment of Thyroid and Breast Surgery, The First Affiliated Hospital, Fujian Medical UniversityDepartment of Thyroid and Breast Surgery, The First Affiliated Hospital, Fujian Medical UniversityDepartment of Thyroid and Breast Surgery, The First Affiliated Hospital, Fujian Medical UniversityDepartment of Thyroid and Breast Surgery, The First Affiliated Hospital, Fujian Medical UniversityDepartment of Thyroid and Breast Surgery, The First Affiliated Hospital, Fujian Medical UniversityCentral Laboratory, Fujian Medical University Union HospitalDepartment of Thyroid and Breast Surgery, The First Affiliated Hospital, Fujian Medical UniversityDepartment of Thyroid and Breast Surgery, The First Affiliated Hospital, Fujian Medical UniversityAbstract N7-methylguanosine (m7G) modification of transfer RNA (tRNA) is essential for the biological functions of tRNAs and has been found to play a regulatory role in a variety of human cancers. However, the biological function of METTL1-mediated m7G tRNA modification in papillary thyroid cancer (PTC) is unclear. Here, we found that METTL1 is significantly upregulated in PTC tissues compared to normal control tissues and is associated with poor PTC prognosis. Functional analysis confirmed that METTL1 promotes the proliferation and metastasis of PTC cells in a manner dependent on its tRNA methyltransferase activity. Mechanistically, METTL1 knockdown leads to a decrease in the abundance of certain m7G-modified tRNAs, which suppresses the m7G tRNA modification-mediated codon-specific translation of TNF-α. Furthermore, exogenous supplementation with TNF-α partially reversed the decrease in the proliferation and metastasis of PTC cells induced by METTL1 deletion. Positive correlations between METTL1, WDR4, and TNF-α expression, which affect the proliferation and metastasis of PTC, were confirmed via analysis of microarrays containing PTC tissues. These results demonstrate the oncogenic role of METTL1-mediated m7G tRNA modification in regulating codon-specific translation efficiency in PTC and suggest that targeting METTL1 may be a promising therapeutic approach for overcoming PTC progression by inhibiting PTC cell proliferation and metastasis.https://doi.org/10.1038/s41419-025-07716-8 |
| spellingShingle | Weiwei Li Ruiwang Xie Huaying Chen Junyu Lin Minjie Zhong Junsi Zhang Shengkai Zheng Cen Jiang Xiangjin Chen Sunwang Xu METTL1-mediated m7G tRNA modification drives papillary thyroid cancer progression and metastasis by regulating the codon-specific translation of TNF-α Cell Death and Disease |
| title | METTL1-mediated m7G tRNA modification drives papillary thyroid cancer progression and metastasis by regulating the codon-specific translation of TNF-α |
| title_full | METTL1-mediated m7G tRNA modification drives papillary thyroid cancer progression and metastasis by regulating the codon-specific translation of TNF-α |
| title_fullStr | METTL1-mediated m7G tRNA modification drives papillary thyroid cancer progression and metastasis by regulating the codon-specific translation of TNF-α |
| title_full_unstemmed | METTL1-mediated m7G tRNA modification drives papillary thyroid cancer progression and metastasis by regulating the codon-specific translation of TNF-α |
| title_short | METTL1-mediated m7G tRNA modification drives papillary thyroid cancer progression and metastasis by regulating the codon-specific translation of TNF-α |
| title_sort | mettl1 mediated m7g trna modification drives papillary thyroid cancer progression and metastasis by regulating the codon specific translation of tnf α |
| url | https://doi.org/10.1038/s41419-025-07716-8 |
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