METTL3 facilitates the progression of cervical cancer by m6A modification-mediated up-regulation of NEK2
Abstract N6-methyladenosine (m6A) is the most prevalent modification found in eukaryotic RNA and played a significant role in various cancers. However, the mechanism by which m6A modification influences cervical cancer (CC) tumorigenesis remains unclear. Therefore, we aim to elucidate the role and m...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-10-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-024-73601-7 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850182080069107712 |
|---|---|
| author | Yilin Guo Yangyang Bai Lu Wang Zhen Xu Nan Zhang Wuliang Wang Hu Zhao |
| author_facet | Yilin Guo Yangyang Bai Lu Wang Zhen Xu Nan Zhang Wuliang Wang Hu Zhao |
| author_sort | Yilin Guo |
| collection | DOAJ |
| description | Abstract N6-methyladenosine (m6A) is the most prevalent modification found in eukaryotic RNA and played a significant role in various cancers. However, the mechanism by which m6A modification influences cervical cancer (CC) tumorigenesis remains unclear. Therefore, we aim to elucidate the role and mechanism of METTL3 in CC progression. In the present study, we observed a significant upregulation of METTL3 in CC tissues and cell lines. Knockdown of METTL3 resulted in reduced growth, migration, and invasion of CC cells, as well as affected apoptosis, while overexpression of METTL3 reversed these effects. Through a combined analysis of meRIP-seq and Ribo-seq data following METTL3 knockdown, NEK2 was identified as a key target of METTL3 in CC cells. Correlation analysis, MeRIP-qPCR, and luciferase reporter assay suggested that METTL3 regulates NEK2 expression through m6A modification. NEK2 synergized with METTL3 to mediate the malignant phenotype of CC cells. The METTL3-NEK2 axis promoted CC progression by activating the Wnt/β-catenin pathway and inhibiting the apoptosis pathway. In conclusion, METTL3 facilitated the malignant progression of CC and contributed to the formation of the METTL3-NEK2 regulatory axis in an m6A-dependent manner, which represented a potential target for CC therapy. |
| format | Article |
| id | doaj-art-7226661610bb4e68a556620fcece951c |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-7226661610bb4e68a556620fcece951c2025-08-20T02:17:45ZengNature PortfolioScientific Reports2045-23222024-10-0114111210.1038/s41598-024-73601-7METTL3 facilitates the progression of cervical cancer by m6A modification-mediated up-regulation of NEK2Yilin Guo0Yangyang Bai1Lu Wang2Zhen Xu3Nan Zhang4Wuliang Wang5Hu Zhao6Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Zhengzhou UniversityDepartment of Urology, Henan Provincial Hospital of Traditional Chinese MedicineDepartment of Gynecology and Obstetrics, The Second Affiliated Hospital of Zhengzhou UniversityDepartment of Gynecology and Obstetrics, The Second Affiliated Hospital of Zhengzhou UniversityDepartment of Gynecology and Obstetrics, The Second Affiliated Hospital of Zhengzhou UniversityDepartment of Gynecology and Obstetrics, The Second Affiliated Hospital of Zhengzhou UniversityDepartment of Gynecology and Obstetrics, The Second Affiliated Hospital of Zhengzhou UniversityAbstract N6-methyladenosine (m6A) is the most prevalent modification found in eukaryotic RNA and played a significant role in various cancers. However, the mechanism by which m6A modification influences cervical cancer (CC) tumorigenesis remains unclear. Therefore, we aim to elucidate the role and mechanism of METTL3 in CC progression. In the present study, we observed a significant upregulation of METTL3 in CC tissues and cell lines. Knockdown of METTL3 resulted in reduced growth, migration, and invasion of CC cells, as well as affected apoptosis, while overexpression of METTL3 reversed these effects. Through a combined analysis of meRIP-seq and Ribo-seq data following METTL3 knockdown, NEK2 was identified as a key target of METTL3 in CC cells. Correlation analysis, MeRIP-qPCR, and luciferase reporter assay suggested that METTL3 regulates NEK2 expression through m6A modification. NEK2 synergized with METTL3 to mediate the malignant phenotype of CC cells. The METTL3-NEK2 axis promoted CC progression by activating the Wnt/β-catenin pathway and inhibiting the apoptosis pathway. In conclusion, METTL3 facilitated the malignant progression of CC and contributed to the formation of the METTL3-NEK2 regulatory axis in an m6A-dependent manner, which represented a potential target for CC therapy.https://doi.org/10.1038/s41598-024-73601-7Cervical cancerN6-methyladenosineMETTL3NEK2 |
| spellingShingle | Yilin Guo Yangyang Bai Lu Wang Zhen Xu Nan Zhang Wuliang Wang Hu Zhao METTL3 facilitates the progression of cervical cancer by m6A modification-mediated up-regulation of NEK2 Scientific Reports Cervical cancer N6-methyladenosine METTL3 NEK2 |
| title | METTL3 facilitates the progression of cervical cancer by m6A modification-mediated up-regulation of NEK2 |
| title_full | METTL3 facilitates the progression of cervical cancer by m6A modification-mediated up-regulation of NEK2 |
| title_fullStr | METTL3 facilitates the progression of cervical cancer by m6A modification-mediated up-regulation of NEK2 |
| title_full_unstemmed | METTL3 facilitates the progression of cervical cancer by m6A modification-mediated up-regulation of NEK2 |
| title_short | METTL3 facilitates the progression of cervical cancer by m6A modification-mediated up-regulation of NEK2 |
| title_sort | mettl3 facilitates the progression of cervical cancer by m6a modification mediated up regulation of nek2 |
| topic | Cervical cancer N6-methyladenosine METTL3 NEK2 |
| url | https://doi.org/10.1038/s41598-024-73601-7 |
| work_keys_str_mv | AT yilinguo mettl3facilitatestheprogressionofcervicalcancerbym6amodificationmediatedupregulationofnek2 AT yangyangbai mettl3facilitatestheprogressionofcervicalcancerbym6amodificationmediatedupregulationofnek2 AT luwang mettl3facilitatestheprogressionofcervicalcancerbym6amodificationmediatedupregulationofnek2 AT zhenxu mettl3facilitatestheprogressionofcervicalcancerbym6amodificationmediatedupregulationofnek2 AT nanzhang mettl3facilitatestheprogressionofcervicalcancerbym6amodificationmediatedupregulationofnek2 AT wuliangwang mettl3facilitatestheprogressionofcervicalcancerbym6amodificationmediatedupregulationofnek2 AT huzhao mettl3facilitatestheprogressionofcervicalcancerbym6amodificationmediatedupregulationofnek2 |