Menin facilitates the cell proliferation of bladder cancer via modulating the TFAP2C/β-catenin axis
Bladder cancer (BLCA) is a common malignant tumor of the urinary system, with significant morbidity and mortality rates worldwide. The MEN1 gene, encoding the menin protein, plays a regulatory role in several cancers. However, the role played by menin in BLCA remains elusive. In this study, our data...
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KeAi Communications Co., Ltd.
2025-11-01
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| Series: | Genes and Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304225000546 |
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| author | Qing Shi Xiang Pan Shiheng Zhang Mengyuan Wu Meiqi Xu Yun-Qi Li Li Zhong Zi-Qi Wang Wanhai Xu Yakun Luo |
| author_facet | Qing Shi Xiang Pan Shiheng Zhang Mengyuan Wu Meiqi Xu Yun-Qi Li Li Zhong Zi-Qi Wang Wanhai Xu Yakun Luo |
| author_sort | Qing Shi |
| collection | DOAJ |
| description | Bladder cancer (BLCA) is a common malignant tumor of the urinary system, with significant morbidity and mortality rates worldwide. The MEN1 gene, encoding the menin protein, plays a regulatory role in several cancers. However, the role played by menin in BLCA remains elusive. In this study, our data demonstrated that the expression of menin was significantly up-regulated in BLCA tissues versus normal tissues, and the high expression of menin was strongly correlated with poor prognosis of BLCA patients. In vitro, silencing MEN1 inhibited cell proliferation and induced cell cycle arrest at the G1/S phase in BLCA cells. Furthermore, RNA sequencing analysis revealed that MEN1 knockdown significantly inhibited the Wnt/β-catenin signaling in BLCA cells. Meanwhile, we further confirmed that β-catenin served as a critical downstream effector of menin in BLCA cells. Mechanically, chromatin immunoprecipitation analysis demonstrated that menin promoted CTNNB1 (catenin beta 1) transcription through binding to the CTNNB1 proximal promoter in BLCA cells. Interestingly, menin collaborated with TFAP2C, a regulator of β-catenin in BLCA cells, to enhance the transcription of the CTNNB1 gene. More intriguingly, BAY-155, a menin molecule inhibitor, inhibited cell growth of BLCA cells both in vitro and in vivo by suppressing the expression of menin, TFAP2C, and β-catenin. Our current work unveils an important role of the menin in triggering the TFAP2C/β-catenin axis, which contributes to cell proliferation of BLCA cells. Therefore, menin might be served as a new therapeutic target for BLCA. |
| format | Article |
| id | doaj-art-ae41dc3dbf984c82889cf5aa0dfe9331 |
| institution | Kabale University |
| issn | 2352-3042 |
| language | English |
| publishDate | 2025-11-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Genes and Diseases |
| spelling | doaj-art-ae41dc3dbf984c82889cf5aa0dfe93312025-08-24T05:12:59ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422025-11-0112610156510.1016/j.gendis.2025.101565Menin facilitates the cell proliferation of bladder cancer via modulating the TFAP2C/β-catenin axisQing Shi0Xiang Pan1Shiheng Zhang2Mengyuan Wu3Meiqi Xu4Yun-Qi Li5Li Zhong6Zi-Qi Wang7Wanhai Xu8Yakun Luo9NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, Heilongjiang 150001, ChinaNHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, Heilongjiang 150001, ChinaChongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Faculty of Basic Medical Sciences, Chongqing Three Gorges Medical College, Wanzhou, Chongqing 404120, ChinaNHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, Heilongjiang 150001, ChinaNHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, Heilongjiang 150001, ChinaNational Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200233, ChinaCentre International de Recherche en Infectiologie (CIRI), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon 69373, FranceNHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, Heilongjiang 150001, China; Department of Urology, The Cancer Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, China; Corresponding author. NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, Heilongjiang 150001, China.NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, Heilongjiang 150001, China; Department of Urology, The Cancer Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, China; Corresponding author. NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, Heilongjiang 150001, China.NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, Heilongjiang 150001, China; Department of Urology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China; Corresponding author. NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, Heilongjiang 150001, China.Bladder cancer (BLCA) is a common malignant tumor of the urinary system, with significant morbidity and mortality rates worldwide. The MEN1 gene, encoding the menin protein, plays a regulatory role in several cancers. However, the role played by menin in BLCA remains elusive. In this study, our data demonstrated that the expression of menin was significantly up-regulated in BLCA tissues versus normal tissues, and the high expression of menin was strongly correlated with poor prognosis of BLCA patients. In vitro, silencing MEN1 inhibited cell proliferation and induced cell cycle arrest at the G1/S phase in BLCA cells. Furthermore, RNA sequencing analysis revealed that MEN1 knockdown significantly inhibited the Wnt/β-catenin signaling in BLCA cells. Meanwhile, we further confirmed that β-catenin served as a critical downstream effector of menin in BLCA cells. Mechanically, chromatin immunoprecipitation analysis demonstrated that menin promoted CTNNB1 (catenin beta 1) transcription through binding to the CTNNB1 proximal promoter in BLCA cells. Interestingly, menin collaborated with TFAP2C, a regulator of β-catenin in BLCA cells, to enhance the transcription of the CTNNB1 gene. More intriguingly, BAY-155, a menin molecule inhibitor, inhibited cell growth of BLCA cells both in vitro and in vivo by suppressing the expression of menin, TFAP2C, and β-catenin. Our current work unveils an important role of the menin in triggering the TFAP2C/β-catenin axis, which contributes to cell proliferation of BLCA cells. Therefore, menin might be served as a new therapeutic target for BLCA.http://www.sciencedirect.com/science/article/pii/S2352304225000546β-cateninBladder cancerCell proliferationMEN1TFAP2CTherapeutic target |
| spellingShingle | Qing Shi Xiang Pan Shiheng Zhang Mengyuan Wu Meiqi Xu Yun-Qi Li Li Zhong Zi-Qi Wang Wanhai Xu Yakun Luo Menin facilitates the cell proliferation of bladder cancer via modulating the TFAP2C/β-catenin axis Genes and Diseases β-catenin Bladder cancer Cell proliferation MEN1 TFAP2C Therapeutic target |
| title | Menin facilitates the cell proliferation of bladder cancer via modulating the TFAP2C/β-catenin axis |
| title_full | Menin facilitates the cell proliferation of bladder cancer via modulating the TFAP2C/β-catenin axis |
| title_fullStr | Menin facilitates the cell proliferation of bladder cancer via modulating the TFAP2C/β-catenin axis |
| title_full_unstemmed | Menin facilitates the cell proliferation of bladder cancer via modulating the TFAP2C/β-catenin axis |
| title_short | Menin facilitates the cell proliferation of bladder cancer via modulating the TFAP2C/β-catenin axis |
| title_sort | menin facilitates the cell proliferation of bladder cancer via modulating the tfap2c β catenin axis |
| topic | β-catenin Bladder cancer Cell proliferation MEN1 TFAP2C Therapeutic target |
| url | http://www.sciencedirect.com/science/article/pii/S2352304225000546 |
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