CLIC3 interacts with NAT10 to inhibit N4-acetylcytidine modification of p21 mRNA and promote bladder cancer progression
Abstract Chromatin accessibility plays important roles in revealing the regulatory networks of gene expression, while its application in bladder cancer is yet to be fully elucidated. Chloride intracellular channel 3 (CLIC3) protein has been reported to be associated with the progression of some tumo...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2024-01-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-023-06373-z |
| _version_ | 1827388069619171328 |
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| author | Yujun Shuai Hui Zhang Changhao Liu Junting Wang Yangkai Jiang Jiayin Sun Xincheng Gao Xiaochen Bo Xingyuan Xiao Xin Liao Chao Huang Hebing Chen Guosong Jiang |
| author_facet | Yujun Shuai Hui Zhang Changhao Liu Junting Wang Yangkai Jiang Jiayin Sun Xincheng Gao Xiaochen Bo Xingyuan Xiao Xin Liao Chao Huang Hebing Chen Guosong Jiang |
| author_sort | Yujun Shuai |
| collection | DOAJ |
| description | Abstract Chromatin accessibility plays important roles in revealing the regulatory networks of gene expression, while its application in bladder cancer is yet to be fully elucidated. Chloride intracellular channel 3 (CLIC3) protein has been reported to be associated with the progression of some tumors, whereas the specific mechanism of CLIC3 in tumor remains unclear. Here, we screened for key genes in bladder cancer through the identification of transcription factor binding site clustered region (TFCR) on the basis of chromatin accessibility and TF motif. CLIC3 was identified by joint profiling of chromatin accessibility data with TCGA database. Clinically, CLIC3 expression was significantly elevated in bladder cancer and was negatively correlated with patient survival. CLIC3 promoted the proliferation of bladder cancer cells by reducing p21 expression in vitro and in vivo. Mechanistically, CLIC3 interacted with NAT10 and inhibited the function of NAT10, resulting in the downregulation of ac4C modification and stability of p21 mRNA. Overall, these findings uncover an novel mechanism of mRNA ac4C modification and CLIC3 may act as a potential therapeutic target for bladder cancer. |
| first_indexed | 2024-03-08T16:11:59Z |
| format | Article |
| id | doaj.art-074eb5a43fb04b9ebbc4d5c1fc923cb3 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-03-08T16:11:59Z |
| publishDate | 2024-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-074eb5a43fb04b9ebbc4d5c1fc923cb32024-01-07T12:49:21ZengNature Publishing GroupCell Death and Disease2041-48892024-01-0115111410.1038/s41419-023-06373-zCLIC3 interacts with NAT10 to inhibit N4-acetylcytidine modification of p21 mRNA and promote bladder cancer progressionYujun Shuai0Hui Zhang1Changhao Liu2Junting Wang3Yangkai Jiang4Jiayin Sun5Xincheng Gao6Xiaochen Bo7Xingyuan Xiao8Xin Liao9Chao Huang10Hebing Chen11Guosong Jiang12Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyInstitute of Health Service and Transfusion MedicineInstitute of Health Service and Transfusion MedicineDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyInstitute of Health Service and Transfusion MedicineDepartment of Urology, Zhongnan Hospital of Wuhan UniversityDepartment of General Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyInstitute of Health Service and Transfusion MedicineDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Chromatin accessibility plays important roles in revealing the regulatory networks of gene expression, while its application in bladder cancer is yet to be fully elucidated. Chloride intracellular channel 3 (CLIC3) protein has been reported to be associated with the progression of some tumors, whereas the specific mechanism of CLIC3 in tumor remains unclear. Here, we screened for key genes in bladder cancer through the identification of transcription factor binding site clustered region (TFCR) on the basis of chromatin accessibility and TF motif. CLIC3 was identified by joint profiling of chromatin accessibility data with TCGA database. Clinically, CLIC3 expression was significantly elevated in bladder cancer and was negatively correlated with patient survival. CLIC3 promoted the proliferation of bladder cancer cells by reducing p21 expression in vitro and in vivo. Mechanistically, CLIC3 interacted with NAT10 and inhibited the function of NAT10, resulting in the downregulation of ac4C modification and stability of p21 mRNA. Overall, these findings uncover an novel mechanism of mRNA ac4C modification and CLIC3 may act as a potential therapeutic target for bladder cancer.https://doi.org/10.1038/s41419-023-06373-z |
| spellingShingle | Yujun Shuai Hui Zhang Changhao Liu Junting Wang Yangkai Jiang Jiayin Sun Xincheng Gao Xiaochen Bo Xingyuan Xiao Xin Liao Chao Huang Hebing Chen Guosong Jiang CLIC3 interacts with NAT10 to inhibit N4-acetylcytidine modification of p21 mRNA and promote bladder cancer progression Cell Death and Disease |
| title | CLIC3 interacts with NAT10 to inhibit N4-acetylcytidine modification of p21 mRNA and promote bladder cancer progression |
| title_full | CLIC3 interacts with NAT10 to inhibit N4-acetylcytidine modification of p21 mRNA and promote bladder cancer progression |
| title_fullStr | CLIC3 interacts with NAT10 to inhibit N4-acetylcytidine modification of p21 mRNA and promote bladder cancer progression |
| title_full_unstemmed | CLIC3 interacts with NAT10 to inhibit N4-acetylcytidine modification of p21 mRNA and promote bladder cancer progression |
| title_short | CLIC3 interacts with NAT10 to inhibit N4-acetylcytidine modification of p21 mRNA and promote bladder cancer progression |
| title_sort | clic3 interacts with nat10 to inhibit n4 acetylcytidine modification of p21 mrna and promote bladder cancer progression |
| url | https://doi.org/10.1038/s41419-023-06373-z |
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