ZNF276 promotes the malignant phenotype of breast carcinoma by activating the CYP1B1-mediated Wnt/β-catenin pathway
Abstract Zinc finger proteins (ZNFs) have been demonstrated to participate extensively in breast cancer progression by functioning as transcription factors, but there are still a variety of ZNFs whose biological mechanisms remain unknown. Here, we show that zinc finger protein 276 (ZNF276) is highly...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-09-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-05223-8 |
| _version_ | 1811273576500690944 |
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| author | Ting Lei Wenwu Zhang Yongyin He Shi Wei Xiaoyu Song Yi Zhu Guoqing Luo Zhenzhan Kuang Guanjie Li Quan Zhou Zhaohui Sun Bin Xiao Linhai Li |
| author_facet | Ting Lei Wenwu Zhang Yongyin He Shi Wei Xiaoyu Song Yi Zhu Guoqing Luo Zhenzhan Kuang Guanjie Li Quan Zhou Zhaohui Sun Bin Xiao Linhai Li |
| author_sort | Ting Lei |
| collection | DOAJ |
| description | Abstract Zinc finger proteins (ZNFs) have been demonstrated to participate extensively in breast cancer progression by functioning as transcription factors, but there are still a variety of ZNFs whose biological mechanisms remain unknown. Here, we show that zinc finger protein 276 (ZNF276) is highly expressed in breast cancer tissues and cell lines. Higher level of ZNF276 correlated with poor prognosis. Gain-of and loss-of function suggested that ZNF276 is essential for the proliferation, migration and invasion of breast cancer cells in vitro and metastasis in vivo. RNA-sequencing and CUT&Tag assay revealed that ZNF276 controlled a variety of growth and metastasis-related genes expression. ZNF276 transcriptionally promoted the expression of CYP1B1 by directly binds to the promoter region of the CYP1B1 through its C2H2 domain. ZNF276 facilitated the translocation of β-catenin from cytoplasm to nucleus through CYP1B1, leading to the upregulation of cyclin D1 and c-Myc, and the activation of the Wnt/β-catenin pathway. Knockdown of CYP1B1 significantly blocked the ZNF276-mediated effects on cell proliferation, migration and invasion. Lastly, ZNF276 interacted with MAGEB2 which enhanced the binding of ZNF276 at the CYP1B1 promoter, promoted CYP1B1 expression and Wnt signaling activation. Collectively, these findings highlight the oncogenic role of ZNF276 on breast cancer cell proliferation and metastasis. Targeting ZNF276/MAGEB2 axis may serve as a potential therapeutic strategy for breast cancer patients. |
| first_indexed | 2024-04-12T23:02:24Z |
| format | Article |
| id | doaj.art-511a0dacc6694d74ac3adbddb9335a34 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-12T23:02:24Z |
| publishDate | 2022-09-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-511a0dacc6694d74ac3adbddb9335a342022-12-22T03:13:02ZengNature Publishing GroupCell Death and Disease2041-48892022-09-0113911510.1038/s41419-022-05223-8ZNF276 promotes the malignant phenotype of breast carcinoma by activating the CYP1B1-mediated Wnt/β-catenin pathwayTing Lei0Wenwu Zhang1Yongyin He2Shi Wei3Xiaoyu Song4Yi Zhu5Guoqing Luo6Zhenzhan Kuang7Guanjie Li8Quan Zhou9Zhaohui Sun10Bin Xiao11Linhai Li12Department of Laboratory Medicine, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s HospitalGuangzhou University of Chinese MedicineDepartment of Laboratory Medicine, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s HospitalDepartment of Laboratory Medicine, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s HospitalDepartment of Laboratory Medicine, General Hospital of Southern Theatre Command of PLADepartment of Laboratory Medicine, General Hospital of Southern Theatre Command of PLADepartment of General Surgery Section 5, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s HospitalDepartment of Laboratory Medicine, General Hospital of Southern Theatre Command of PLADepartment of General Surgery Section 5, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s HospitalDepartment of Laboratory Medicine, General Hospital of Southern Theatre Command of PLADepartment of Laboratory Medicine, General Hospital of Southern Theatre Command of PLADepartment of Laboratory Medicine, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s HospitalDepartment of Laboratory Medicine, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s HospitalAbstract Zinc finger proteins (ZNFs) have been demonstrated to participate extensively in breast cancer progression by functioning as transcription factors, but there are still a variety of ZNFs whose biological mechanisms remain unknown. Here, we show that zinc finger protein 276 (ZNF276) is highly expressed in breast cancer tissues and cell lines. Higher level of ZNF276 correlated with poor prognosis. Gain-of and loss-of function suggested that ZNF276 is essential for the proliferation, migration and invasion of breast cancer cells in vitro and metastasis in vivo. RNA-sequencing and CUT&Tag assay revealed that ZNF276 controlled a variety of growth and metastasis-related genes expression. ZNF276 transcriptionally promoted the expression of CYP1B1 by directly binds to the promoter region of the CYP1B1 through its C2H2 domain. ZNF276 facilitated the translocation of β-catenin from cytoplasm to nucleus through CYP1B1, leading to the upregulation of cyclin D1 and c-Myc, and the activation of the Wnt/β-catenin pathway. Knockdown of CYP1B1 significantly blocked the ZNF276-mediated effects on cell proliferation, migration and invasion. Lastly, ZNF276 interacted with MAGEB2 which enhanced the binding of ZNF276 at the CYP1B1 promoter, promoted CYP1B1 expression and Wnt signaling activation. Collectively, these findings highlight the oncogenic role of ZNF276 on breast cancer cell proliferation and metastasis. Targeting ZNF276/MAGEB2 axis may serve as a potential therapeutic strategy for breast cancer patients.https://doi.org/10.1038/s41419-022-05223-8 |
| spellingShingle | Ting Lei Wenwu Zhang Yongyin He Shi Wei Xiaoyu Song Yi Zhu Guoqing Luo Zhenzhan Kuang Guanjie Li Quan Zhou Zhaohui Sun Bin Xiao Linhai Li ZNF276 promotes the malignant phenotype of breast carcinoma by activating the CYP1B1-mediated Wnt/β-catenin pathway Cell Death and Disease |
| title | ZNF276 promotes the malignant phenotype of breast carcinoma by activating the CYP1B1-mediated Wnt/β-catenin pathway |
| title_full | ZNF276 promotes the malignant phenotype of breast carcinoma by activating the CYP1B1-mediated Wnt/β-catenin pathway |
| title_fullStr | ZNF276 promotes the malignant phenotype of breast carcinoma by activating the CYP1B1-mediated Wnt/β-catenin pathway |
| title_full_unstemmed | ZNF276 promotes the malignant phenotype of breast carcinoma by activating the CYP1B1-mediated Wnt/β-catenin pathway |
| title_short | ZNF276 promotes the malignant phenotype of breast carcinoma by activating the CYP1B1-mediated Wnt/β-catenin pathway |
| title_sort | znf276 promotes the malignant phenotype of breast carcinoma by activating the cyp1b1 mediated wnt β catenin pathway |
| url | https://doi.org/10.1038/s41419-022-05223-8 |
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