A potassium-chloride co-transporter promotes tumor progression and castration resistance of prostate cancer through m6A reader YTHDC1
Abstract SLC12A5, a neuron-specific potassium-chloride co-transporter, has been reported to promote tumor progression, however, the underlying mechanism remains unclear. Here we report that SLC12A5 functions as an oncogene to promote tumor progression and castration resistance of prostate cancer thr...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-01-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-05544-8 |
| _version_ | 1797958488215781376 |
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| author | Shuai Yuan Shao-Hua He Lu-Yao Li Shu Xi Hong Weng Jin-Hui Zhang Dan-Qi Wang Meng-Meng Guo Haozhe Zhang Shuang-Ying Wang Dao-Jing Ming Meng-Yang Liu Hailiang Hu Xian-Tao Zeng |
| author_facet | Shuai Yuan Shao-Hua He Lu-Yao Li Shu Xi Hong Weng Jin-Hui Zhang Dan-Qi Wang Meng-Meng Guo Haozhe Zhang Shuang-Ying Wang Dao-Jing Ming Meng-Yang Liu Hailiang Hu Xian-Tao Zeng |
| author_sort | Shuai Yuan |
| collection | DOAJ |
| description | Abstract SLC12A5, a neuron-specific potassium-chloride co-transporter, has been reported to promote tumor progression, however, the underlying mechanism remains unclear. Here we report that SLC12A5 functions as an oncogene to promote tumor progression and castration resistance of prostate cancer through the N6-methyladenosine (m6A) reader YTHDC1 and the transcription factor HOXB13. We have shown that the level of SLC12A5 was increased in prostate cancer, in comparison to its normal counterparts, and further elevated in castration-resistant prostate cancer (CRPC). The enhanced expression of SLC12A5 mRNA was associated with neuroendocrine prostate cancer (NEPC) progression and poor survival in prostate cancer. Furthermore, we demonstrated that SLC12A5 promoted the castration resistance development of prostate cancer in addition to the cell proliferation and migration. Interestingly, SLC12A5 was detected in the cell nucleus and formed a complex with nuclear m6A reader YTHDC1, which in turn upregulated HOXB13 to promote the prostate cancer progression. Therefore, our findings reveal a mechanism that how the potassium-chloride cotransporter SLC12A5 promotes the tumor progression and provide a therapeutic opportunity for prostate cancer to apply the neurological disorder drug SLC12A5 inhibitors. |
| first_indexed | 2024-04-11T00:19:48Z |
| format | Article |
| id | doaj.art-80607065e5424b5881390843867ec190 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-11T00:19:48Z |
| publishDate | 2023-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-80607065e5424b5881390843867ec1902023-01-08T12:22:07ZengNature Publishing GroupCell Death and Disease2041-48892023-01-0114111110.1038/s41419-022-05544-8A potassium-chloride co-transporter promotes tumor progression and castration resistance of prostate cancer through m6A reader YTHDC1Shuai Yuan0Shao-Hua He1Lu-Yao Li2Shu Xi3Hong Weng4Jin-Hui Zhang5Dan-Qi Wang6Meng-Meng Guo7Haozhe Zhang8Shuang-Ying Wang9Dao-Jing Ming10Meng-Yang Liu11Hailiang Hu12Xian-Tao Zeng13Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan UniversityCenter for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan UniversityCenter for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan UniversityCenter for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan UniversityCenter for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan UniversityCenter for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan UniversityCenter for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan UniversityCenter for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan UniversityDepartment of Biochemistry, School of Medicine, Southern University of Science and TechnologyCenter for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan UniversityCenter for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan UniversityCenter for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan UniversityDepartment of Biochemistry, School of Medicine, Southern University of Science and TechnologyCenter for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan UniversityAbstract SLC12A5, a neuron-specific potassium-chloride co-transporter, has been reported to promote tumor progression, however, the underlying mechanism remains unclear. Here we report that SLC12A5 functions as an oncogene to promote tumor progression and castration resistance of prostate cancer through the N6-methyladenosine (m6A) reader YTHDC1 and the transcription factor HOXB13. We have shown that the level of SLC12A5 was increased in prostate cancer, in comparison to its normal counterparts, and further elevated in castration-resistant prostate cancer (CRPC). The enhanced expression of SLC12A5 mRNA was associated with neuroendocrine prostate cancer (NEPC) progression and poor survival in prostate cancer. Furthermore, we demonstrated that SLC12A5 promoted the castration resistance development of prostate cancer in addition to the cell proliferation and migration. Interestingly, SLC12A5 was detected in the cell nucleus and formed a complex with nuclear m6A reader YTHDC1, which in turn upregulated HOXB13 to promote the prostate cancer progression. Therefore, our findings reveal a mechanism that how the potassium-chloride cotransporter SLC12A5 promotes the tumor progression and provide a therapeutic opportunity for prostate cancer to apply the neurological disorder drug SLC12A5 inhibitors.https://doi.org/10.1038/s41419-022-05544-8 |
| spellingShingle | Shuai Yuan Shao-Hua He Lu-Yao Li Shu Xi Hong Weng Jin-Hui Zhang Dan-Qi Wang Meng-Meng Guo Haozhe Zhang Shuang-Ying Wang Dao-Jing Ming Meng-Yang Liu Hailiang Hu Xian-Tao Zeng A potassium-chloride co-transporter promotes tumor progression and castration resistance of prostate cancer through m6A reader YTHDC1 Cell Death and Disease |
| title | A potassium-chloride co-transporter promotes tumor progression and castration resistance of prostate cancer through m6A reader YTHDC1 |
| title_full | A potassium-chloride co-transporter promotes tumor progression and castration resistance of prostate cancer through m6A reader YTHDC1 |
| title_fullStr | A potassium-chloride co-transporter promotes tumor progression and castration resistance of prostate cancer through m6A reader YTHDC1 |
| title_full_unstemmed | A potassium-chloride co-transporter promotes tumor progression and castration resistance of prostate cancer through m6A reader YTHDC1 |
| title_short | A potassium-chloride co-transporter promotes tumor progression and castration resistance of prostate cancer through m6A reader YTHDC1 |
| title_sort | potassium chloride co transporter promotes tumor progression and castration resistance of prostate cancer through m6a reader ythdc1 |
| url | https://doi.org/10.1038/s41419-022-05544-8 |
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