A Potassium-chloride Co-transporter Promotes Tumor Progression and Castration Resistance of Prostate Cancer Through MA Reader YTHDC1

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2023 Jan 7

PMID 36609444

Authors

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

Affiliations

Soon will be listed here.

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 (mA) 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 mA 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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