METTL1 coordinates cutaneous squamous cell carcinoma progression via the m7G modification of the ATF4 mRNA
Abstract Methyltransferase-like 1 (METTL1)-mediated m7G modification is a common occurrence in various RNA species, including mRNAs, tRNAs, rRNAs, and miRNAs. Recent evidence suggests that this modification is linked to the development of several cancers, making it a promising target for cancer ther...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2025-01-01
|
| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-025-02304-3 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832571974394576896 |
|---|---|
| author | Xinru Zhang Tong Chen Fanrong Zhang Huanhuan Shi Xiang Li Zhijuan Wang Dong Wang Chao Hou |
| author_facet | Xinru Zhang Tong Chen Fanrong Zhang Huanhuan Shi Xiang Li Zhijuan Wang Dong Wang Chao Hou |
| author_sort | Xinru Zhang |
| collection | DOAJ |
| description | Abstract Methyltransferase-like 1 (METTL1)-mediated m7G modification is a common occurrence in various RNA species, including mRNAs, tRNAs, rRNAs, and miRNAs. Recent evidence suggests that this modification is linked to the development of several cancers, making it a promising target for cancer therapy. However, the specific role of m7G modification in cutaneous squamous cell carcinoma (cSCC) is not well understood. In this study, we observed conspicuously elevated levels of METTL1 in cSCC tumors and cell lines. Inhibiting METTL1 led to reduced survival, migration, invasion, and xenograft tumor growth in cSCC cells. Mechanistically, through a combination of RNA sequencing, m7G methylated immunoprecipitation (MeRIP)-qPCR, and mRNA stability assays, we discovered that METTL1 is responsible for the m7G modification of ATF4 mRNA, leading to increased expression of ATF4. Importantly, we demonstrated that this modification is dependent on the methyltransferase activity of METTL1. Additionally, we observed a positive association between ATF4 expression and METTL1 levels in cSCC tumors. Intriguingly, restoring ATF4 expression in cSCC cells not only promoted glycolysis but also reversed the anti-tumor effects of METTL1 knockdown. In conclusion, our results underscore the critical role of METTL1 and m7G modification in cSCC tumorigenesis, suggesting a promising target for future cSCC therapies. |
| format | Article |
| id | doaj-art-055315089b8c43e0b94aaffb7803b915 |
| 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-055315089b8c43e0b94aaffb7803b9152025-02-02T12:08:52ZengNature Publishing GroupCell Death Discovery2058-77162025-01-0111111510.1038/s41420-025-02304-3METTL1 coordinates cutaneous squamous cell carcinoma progression via the m7G modification of the ATF4 mRNAXinru Zhang0Tong Chen1Fanrong Zhang2Huanhuan Shi3Xiang Li4Zhijuan Wang5Dong Wang6Chao Hou7School of Basic Medical Sciences, Anhui Medical UniversitySchool of Basic Medical Sciences, Anhui Medical UniversitySchool of Basic Medical Sciences, Anhui Medical UniversitySchool of Basic Medical Sciences, Anhui Medical UniversityThe First Affiliated Hospital of Anhui Medical UniversityThe Second Affiliated Hospital of Anhui Medical UniversitySchool of Basic Medical Sciences, Anhui Medical UniversitySchool of Basic Medical Sciences, Anhui Medical UniversityAbstract Methyltransferase-like 1 (METTL1)-mediated m7G modification is a common occurrence in various RNA species, including mRNAs, tRNAs, rRNAs, and miRNAs. Recent evidence suggests that this modification is linked to the development of several cancers, making it a promising target for cancer therapy. However, the specific role of m7G modification in cutaneous squamous cell carcinoma (cSCC) is not well understood. In this study, we observed conspicuously elevated levels of METTL1 in cSCC tumors and cell lines. Inhibiting METTL1 led to reduced survival, migration, invasion, and xenograft tumor growth in cSCC cells. Mechanistically, through a combination of RNA sequencing, m7G methylated immunoprecipitation (MeRIP)-qPCR, and mRNA stability assays, we discovered that METTL1 is responsible for the m7G modification of ATF4 mRNA, leading to increased expression of ATF4. Importantly, we demonstrated that this modification is dependent on the methyltransferase activity of METTL1. Additionally, we observed a positive association between ATF4 expression and METTL1 levels in cSCC tumors. Intriguingly, restoring ATF4 expression in cSCC cells not only promoted glycolysis but also reversed the anti-tumor effects of METTL1 knockdown. In conclusion, our results underscore the critical role of METTL1 and m7G modification in cSCC tumorigenesis, suggesting a promising target for future cSCC therapies.https://doi.org/10.1038/s41420-025-02304-3 |
| spellingShingle | Xinru Zhang Tong Chen Fanrong Zhang Huanhuan Shi Xiang Li Zhijuan Wang Dong Wang Chao Hou METTL1 coordinates cutaneous squamous cell carcinoma progression via the m7G modification of the ATF4 mRNA Cell Death Discovery |
| title | METTL1 coordinates cutaneous squamous cell carcinoma progression via the m7G modification of the ATF4 mRNA |
| title_full | METTL1 coordinates cutaneous squamous cell carcinoma progression via the m7G modification of the ATF4 mRNA |
| title_fullStr | METTL1 coordinates cutaneous squamous cell carcinoma progression via the m7G modification of the ATF4 mRNA |
| title_full_unstemmed | METTL1 coordinates cutaneous squamous cell carcinoma progression via the m7G modification of the ATF4 mRNA |
| title_short | METTL1 coordinates cutaneous squamous cell carcinoma progression via the m7G modification of the ATF4 mRNA |
| title_sort | mettl1 coordinates cutaneous squamous cell carcinoma progression via the m7g modification of the atf4 mrna |
| url | https://doi.org/10.1038/s41420-025-02304-3 |
| work_keys_str_mv | AT xinruzhang mettl1coordinatescutaneoussquamouscellcarcinomaprogressionviathem7gmodificationoftheatf4mrna AT tongchen mettl1coordinatescutaneoussquamouscellcarcinomaprogressionviathem7gmodificationoftheatf4mrna AT fanrongzhang mettl1coordinatescutaneoussquamouscellcarcinomaprogressionviathem7gmodificationoftheatf4mrna AT huanhuanshi mettl1coordinatescutaneoussquamouscellcarcinomaprogressionviathem7gmodificationoftheatf4mrna AT xiangli mettl1coordinatescutaneoussquamouscellcarcinomaprogressionviathem7gmodificationoftheatf4mrna AT zhijuanwang mettl1coordinatescutaneoussquamouscellcarcinomaprogressionviathem7gmodificationoftheatf4mrna AT dongwang mettl1coordinatescutaneoussquamouscellcarcinomaprogressionviathem7gmodificationoftheatf4mrna AT chaohou mettl1coordinatescutaneoussquamouscellcarcinomaprogressionviathem7gmodificationoftheatf4mrna |