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A potassium-chloride co-transporter promotes tumor progression and castration resistance of prostate cancer through m(6)A reader YTHDC1

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...

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Autores principales: Yuan, Shuai, He, Shao-Hua, Li, Lu-Yao, Xi, Shu, Weng, Hong, Zhang, Jin-Hui, Wang, Dan-Qi, Guo, Meng-Meng, Zhang, Haozhe, Wang, Shuang-Ying, Ming, Dao-Jing, Liu, Meng-Yang, Hu, Hailiang, Zeng, Xian-Tao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9822915/
https://www.ncbi.nlm.nih.gov/pubmed/36609444
http://dx.doi.org/10.1038/s41419-022-05544-8
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author Yuan, Shuai
He, Shao-Hua
Li, Lu-Yao
Xi, Shu
Weng, Hong
Zhang, Jin-Hui
Wang, Dan-Qi
Guo, Meng-Meng
Zhang, Haozhe
Wang, Shuang-Ying
Ming, Dao-Jing
Liu, Meng-Yang
Hu, Hailiang
Zeng, Xian-Tao
author_facet Yuan, Shuai
He, Shao-Hua
Li, Lu-Yao
Xi, Shu
Weng, Hong
Zhang, Jin-Hui
Wang, Dan-Qi
Guo, Meng-Meng
Zhang, Haozhe
Wang, Shuang-Ying
Ming, Dao-Jing
Liu, Meng-Yang
Hu, Hailiang
Zeng, Xian-Tao
author_sort Yuan, Shuai
collection PubMed
description 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 (m(6)A) 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 m(6)A 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.
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spelling pubmed-98229152023-01-08 A potassium-chloride co-transporter promotes tumor progression and castration resistance of prostate cancer through m(6)A reader YTHDC1 Yuan, Shuai He, Shao-Hua Li, Lu-Yao Xi, Shu Weng, Hong Zhang, Jin-Hui Wang, Dan-Qi Guo, Meng-Meng Zhang, Haozhe Wang, Shuang-Ying Ming, Dao-Jing Liu, Meng-Yang Hu, Hailiang Zeng, Xian-Tao Cell Death Dis Article 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 (m(6)A) 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 m(6)A 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. Nature Publishing Group UK 2023-01-06 /pmc/articles/PMC9822915/ /pubmed/36609444 http://dx.doi.org/10.1038/s41419-022-05544-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Yuan, Shuai
He, Shao-Hua
Li, Lu-Yao
Xi, Shu
Weng, Hong
Zhang, Jin-Hui
Wang, Dan-Qi
Guo, Meng-Meng
Zhang, Haozhe
Wang, Shuang-Ying
Ming, Dao-Jing
Liu, Meng-Yang
Hu, Hailiang
Zeng, Xian-Tao
A potassium-chloride co-transporter promotes tumor progression and castration resistance of prostate cancer through m(6)A reader YTHDC1
title A potassium-chloride co-transporter promotes tumor progression and castration resistance of prostate cancer through m(6)A reader YTHDC1
title_full A potassium-chloride co-transporter promotes tumor progression and castration resistance of prostate cancer through m(6)A reader YTHDC1
title_fullStr A potassium-chloride co-transporter promotes tumor progression and castration resistance of prostate cancer through m(6)A reader YTHDC1
title_full_unstemmed A potassium-chloride co-transporter promotes tumor progression and castration resistance of prostate cancer through m(6)A reader YTHDC1
title_short A potassium-chloride co-transporter promotes tumor progression and castration resistance of prostate cancer through m(6)A reader YTHDC1
title_sort potassium-chloride co-transporter promotes tumor progression and castration resistance of prostate cancer through m(6)a reader ythdc1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9822915/
https://www.ncbi.nlm.nih.gov/pubmed/36609444
http://dx.doi.org/10.1038/s41419-022-05544-8
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