Proteomics analysis reveals FEN1 as a promising therapeutic target against small cell neuroendocrine carcinoma of the cervix
Abstract Small cell neuroendocrine carcinoma of the cervix (SCNECC) is a rare, aggressive cervical cancer with poor prognosis. This study explored molecular drivers of SCNECC progression and identified potential therapeutic targets. Proteomic analysis was conducted to identify differentially express...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-12892-w |
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| author | Jianbing Liu Meiying Zhong Kai Yang Jinjuan Wang Haixia Ma Wei Wang Lin Sun Lingling Liu Jing Xu Xiaohua Cui Jianqing Hao Li Li |
| author_facet | Jianbing Liu Meiying Zhong Kai Yang Jinjuan Wang Haixia Ma Wei Wang Lin Sun Lingling Liu Jing Xu Xiaohua Cui Jianqing Hao Li Li |
| author_sort | Jianbing Liu |
| collection | DOAJ |
| description | Abstract Small cell neuroendocrine carcinoma of the cervix (SCNECC) is a rare, aggressive cervical cancer with poor prognosis. This study explored molecular drivers of SCNECC progression and identified potential therapeutic targets. Proteomic analysis was conducted to identify differentially expressed proteins (DEPs) in SCNECC. Subsequent GO and KEGG enrichment analyses were performed to delineate key DEPs. Functional assays, including CCK-8, colony formation, cell cycle, and apoptosis assays, were conducted to assess the roles of target genes. Expression levels of target genes were validated using qRT-PCR, western blot, and immunohistochemistry (IHC). Proteomic profiling revealed 2333 DEPs in SCNECC, comprising 2168 upregulated and 165 downregulated proteins. GO and KEGG analyses revealed that the upregulated DEPs were predominantly enriched in processes occurring within the cell nucleus, such as DNA replication, reflecting heightened proliferative activity in SCNECC. IHC confirmed FEN1 overexpression. Functional assays showed that FEN1 knockdown suppressed cell viability, colony formation, and cell cycle, promoted apoptosis, and impeded tumor growth in mice. SC13, a FEN1 inhibitor, also had similar effects. Furthermore, silencing FEN1 markedly reduced PIK3CA, PCNA, and BCL-2 levels, while elevating Caspase-9 expression. CONCLUSION: FEN1 overexpression fuels SCNECC progression via PCNA regulation, positioning FEN1 as a promising SCNECC therapeutic target. |
| format | Article |
| id | doaj-art-9f87ee4fba734b35b5f37e0a86de34fb |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-9f87ee4fba734b35b5f37e0a86de34fb2025-08-20T04:01:52ZengNature PortfolioScientific Reports2045-23222025-07-0115111610.1038/s41598-025-12892-wProteomics analysis reveals FEN1 as a promising therapeutic target against small cell neuroendocrine carcinoma of the cervixJianbing Liu0Meiying Zhong1Kai Yang2Jinjuan Wang3Haixia Ma4Wei Wang5Lin Sun6Lingling Liu7Jing Xu8Xiaohua Cui9Jianqing Hao10Li Li11School of Basic Medical Sciences, Key Laboratory of Cellular Physiology(Shanxi Medical University, Ministry of Education), Shanxi Medical UniversitySchool of Basic Medical Sciences, Key Laboratory of Cellular Physiology(Shanxi Medical University, Ministry of Education), Shanxi Medical UniversitySchool of Basic Medical Sciences, Key Laboratory of Cellular Physiology(Shanxi Medical University, Ministry of Education), Shanxi Medical UniversitySchool of Basic Medical Sciences, Key Laboratory of Cellular Physiology(Shanxi Medical University, Ministry of Education), Shanxi Medical UniversityDepartment of Pathology, Shanxi Province Cancer HospitalDepartments of Obstetrics and Gynecology, the Second Hospital of Shanxi Medical UniversityShanxi Second People’s Hospital, General Surgery DepartmentPathology Department, Third Hospital of Shanxi Medical UniversitySchool of Basic Medical Sciences, Key Laboratory of Cellular Physiology(Shanxi Medical University, Ministry of Education), Shanxi Medical UniversitySchool of Basic Medical Sciences, Key Laboratory of Cellular Physiology(Shanxi Medical University, Ministry of Education), Shanxi Medical UniversitySchool of Basic Medical Sciences, Key Laboratory of Cellular Physiology(Shanxi Medical University, Ministry of Education), Shanxi Medical UniversitySchool of Basic Medical Sciences, Key Laboratory of Cellular Physiology(Shanxi Medical University, Ministry of Education), Shanxi Medical UniversityAbstract Small cell neuroendocrine carcinoma of the cervix (SCNECC) is a rare, aggressive cervical cancer with poor prognosis. This study explored molecular drivers of SCNECC progression and identified potential therapeutic targets. Proteomic analysis was conducted to identify differentially expressed proteins (DEPs) in SCNECC. Subsequent GO and KEGG enrichment analyses were performed to delineate key DEPs. Functional assays, including CCK-8, colony formation, cell cycle, and apoptosis assays, were conducted to assess the roles of target genes. Expression levels of target genes were validated using qRT-PCR, western blot, and immunohistochemistry (IHC). Proteomic profiling revealed 2333 DEPs in SCNECC, comprising 2168 upregulated and 165 downregulated proteins. GO and KEGG analyses revealed that the upregulated DEPs were predominantly enriched in processes occurring within the cell nucleus, such as DNA replication, reflecting heightened proliferative activity in SCNECC. IHC confirmed FEN1 overexpression. Functional assays showed that FEN1 knockdown suppressed cell viability, colony formation, and cell cycle, promoted apoptosis, and impeded tumor growth in mice. SC13, a FEN1 inhibitor, also had similar effects. Furthermore, silencing FEN1 markedly reduced PIK3CA, PCNA, and BCL-2 levels, while elevating Caspase-9 expression. CONCLUSION: FEN1 overexpression fuels SCNECC progression via PCNA regulation, positioning FEN1 as a promising SCNECC therapeutic target.https://doi.org/10.1038/s41598-025-12892-wSmall cell neuroendocrine carcinoma of the cervix (SCNECC)Proteomic profilingFEN1 proteinTherapeutic target |
| spellingShingle | Jianbing Liu Meiying Zhong Kai Yang Jinjuan Wang Haixia Ma Wei Wang Lin Sun Lingling Liu Jing Xu Xiaohua Cui Jianqing Hao Li Li Proteomics analysis reveals FEN1 as a promising therapeutic target against small cell neuroendocrine carcinoma of the cervix Scientific Reports Small cell neuroendocrine carcinoma of the cervix (SCNECC) Proteomic profiling FEN1 protein Therapeutic target |
| title | Proteomics analysis reveals FEN1 as a promising therapeutic target against small cell neuroendocrine carcinoma of the cervix |
| title_full | Proteomics analysis reveals FEN1 as a promising therapeutic target against small cell neuroendocrine carcinoma of the cervix |
| title_fullStr | Proteomics analysis reveals FEN1 as a promising therapeutic target against small cell neuroendocrine carcinoma of the cervix |
| title_full_unstemmed | Proteomics analysis reveals FEN1 as a promising therapeutic target against small cell neuroendocrine carcinoma of the cervix |
| title_short | Proteomics analysis reveals FEN1 as a promising therapeutic target against small cell neuroendocrine carcinoma of the cervix |
| title_sort | proteomics analysis reveals fen1 as a promising therapeutic target against small cell neuroendocrine carcinoma of the cervix |
| topic | Small cell neuroendocrine carcinoma of the cervix (SCNECC) Proteomic profiling FEN1 protein Therapeutic target |
| url | https://doi.org/10.1038/s41598-025-12892-w |
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