CircZFR/YTHDF3 axis drives lymph node metastasis in cervical cancer via FASN translation
Abstract Background Lymph node metastasis is a key driver of poor outcomes in cervical cancer. However, the molecular mechanisms of circular RNAs (circRNAs) driving cervical cancer lymph node metastasis remain unclear. Methods We identified circZFR, fatty acid synthase (FASN) and YTH N6-methyladenos...
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BMC
2025-08-01
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| Series: | Molecular Cancer |
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| Online Access: | https://doi.org/10.1186/s12943-025-02424-5 |
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| author | Mingyi Zhou Yan Gao Yong Zhang Lian He Bo Gao Yue Zhang Francois X. Claret George A. Calin Danbo Wang |
| author_facet | Mingyi Zhou Yan Gao Yong Zhang Lian He Bo Gao Yue Zhang Francois X. Claret George A. Calin Danbo Wang |
| author_sort | Mingyi Zhou |
| collection | DOAJ |
| description | Abstract Background Lymph node metastasis is a key driver of poor outcomes in cervical cancer. However, the molecular mechanisms of circular RNAs (circRNAs) driving cervical cancer lymph node metastasis remain unclear. Methods We identified circZFR, fatty acid synthase (FASN) and YTH N6-methyladenosine RNA binding protein F3 (YTHDF3) protein expression in the cervical cancer patients with long and short disease-free survival (DFS). Functional experiments were performed to investigate the function of circZFR, FASN and YTHDF3 on cell migration and invasion. MeRIP-qPCR, RNA pulldown, RNA Immunoprecipitation (RIP), and Co-Immunoprecipitation (Co-IP) assays were executed to investigate the mechanism of circZFR regulating FASN protein expression. Results Our study reveals that elevated FASN protein is closely linked to metastasis and reduced survival, and identified a regulatory mechanism involving circular RNAs. We identified circZFR as a crucial regulator, significantly enhancing FASN protein expression. CircZFR overexpression was significantly correlated with accelerated lymph node metastasis and shortened DFS. Mechanistically, circZFR binds to the m6A reader protein YTHDF3, facilitating m6A recognition on FASN mRNA and recruiting the translation initiator eIF4A3, thereby boosting FASN translation. Conclusions These findings establish circZFR as a pivotal driver of cervical cancer progression and highlight its inhibition as a promising therapeutic strategy. |
| format | Article |
| id | doaj-art-7e24a41b7a6c4c50adcc365e7a1af4de |
| institution | Kabale University |
| issn | 1476-4598 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
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| series | Molecular Cancer |
| spelling | doaj-art-7e24a41b7a6c4c50adcc365e7a1af4de2025-08-24T11:11:18ZengBMCMolecular Cancer1476-45982025-08-0124111510.1186/s12943-025-02424-5CircZFR/YTHDF3 axis drives lymph node metastasis in cervical cancer via FASN translationMingyi Zhou0Yan Gao1Yong Zhang2Lian He3Bo Gao4Yue Zhang5Francois X. Claret6George A. Calin7Danbo Wang8Department of Gynecology, Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital & InstituteDepartment of Gynecology, Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital & InstituteDepartment of Pathology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & InstituteDepartment of Pathology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & InstituteDepartment of Pathology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & InstituteDepartment of Pathology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & InstituteDepartment of Systems Biology, University of Texas MD Anderson Cancer CenterDepartment of Translational Molecular Pathology, Center for RNA Interference and Non-Coding RNAs, University of Texas MD Anderson Cancer CenterDepartment of Gynecology, Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital & InstituteAbstract Background Lymph node metastasis is a key driver of poor outcomes in cervical cancer. However, the molecular mechanisms of circular RNAs (circRNAs) driving cervical cancer lymph node metastasis remain unclear. Methods We identified circZFR, fatty acid synthase (FASN) and YTH N6-methyladenosine RNA binding protein F3 (YTHDF3) protein expression in the cervical cancer patients with long and short disease-free survival (DFS). Functional experiments were performed to investigate the function of circZFR, FASN and YTHDF3 on cell migration and invasion. MeRIP-qPCR, RNA pulldown, RNA Immunoprecipitation (RIP), and Co-Immunoprecipitation (Co-IP) assays were executed to investigate the mechanism of circZFR regulating FASN protein expression. Results Our study reveals that elevated FASN protein is closely linked to metastasis and reduced survival, and identified a regulatory mechanism involving circular RNAs. We identified circZFR as a crucial regulator, significantly enhancing FASN protein expression. CircZFR overexpression was significantly correlated with accelerated lymph node metastasis and shortened DFS. Mechanistically, circZFR binds to the m6A reader protein YTHDF3, facilitating m6A recognition on FASN mRNA and recruiting the translation initiator eIF4A3, thereby boosting FASN translation. Conclusions These findings establish circZFR as a pivotal driver of cervical cancer progression and highlight its inhibition as a promising therapeutic strategy.https://doi.org/10.1186/s12943-025-02424-5Prognostic markersLymph node metastasisYTH N6-methyladenosine RNA binding protein F3 (YTHDF3)Fatty acid synthase (FASN) |
| spellingShingle | Mingyi Zhou Yan Gao Yong Zhang Lian He Bo Gao Yue Zhang Francois X. Claret George A. Calin Danbo Wang CircZFR/YTHDF3 axis drives lymph node metastasis in cervical cancer via FASN translation Molecular Cancer Prognostic markers Lymph node metastasis YTH N6-methyladenosine RNA binding protein F3 (YTHDF3) Fatty acid synthase (FASN) |
| title | CircZFR/YTHDF3 axis drives lymph node metastasis in cervical cancer via FASN translation |
| title_full | CircZFR/YTHDF3 axis drives lymph node metastasis in cervical cancer via FASN translation |
| title_fullStr | CircZFR/YTHDF3 axis drives lymph node metastasis in cervical cancer via FASN translation |
| title_full_unstemmed | CircZFR/YTHDF3 axis drives lymph node metastasis in cervical cancer via FASN translation |
| title_short | CircZFR/YTHDF3 axis drives lymph node metastasis in cervical cancer via FASN translation |
| title_sort | circzfr ythdf3 axis drives lymph node metastasis in cervical cancer via fasn translation |
| topic | Prognostic markers Lymph node metastasis YTH N6-methyladenosine RNA binding protein F3 (YTHDF3) Fatty acid synthase (FASN) |
| url | https://doi.org/10.1186/s12943-025-02424-5 |
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