| Autor: |
Ching-Hsin Chang, Wayne W. Yeh, Ting-Yu Cheng, Yun-Li Luo, Mel Campbell, Tse-Chun Kuo, Tsai-Wen Shen, Yung-Chih Hong, Cheng-Han Tsai, Yu-Ching Peng, Chin-Chen Pan, Muh-Hwa Yang, Jean-Chen Shih, Hsing-Jien Kung, William J. Huang, Pei-Ching Chang, Tzu-Ping Lin |
| Rok vydání: |
2022 |
| Popis: |
Background Lineage plasticity is recognized as a treatment-induced resistance mechanism in prostate cancer (PCa) and contributes to the development of neuroendocrine prostate cancer (NEPC), a lethal variant of castration-resistant prostate cancer (CRPC), that is increasing in the era of second-generation anti-hormonal therapy. At present, there are no effective treatments for NEPC. Conclusions and perspectives Following our long-standing interest in studying RE1-silencing transcription factor (REST), a pivotal repressor of neuroendocrine differentiation (NED), we conducted a siRNA screening targeting 147 REST-repressing long non-coding RNAs (lncRNAs) and identified prostate cancer transcript-neuroendocrine 1 (PCAT-NE1) as a novel lncRNA that induces NED through activating autophagy signaling, crucial for NED of prostate adenocarcinoma cell. Analyses of clinical data and samples indicate that PCAT-NE1 is elevated in NEPC. Through gain- and loss-of-function experiments, we find that PCAT-NE1 promotes NED. Mechanistically, PCAT-NE1 acts as a competing endogenous RNA (ceRNA) that sponge hsa-miR-6889-3p, leading to the up-regulation of autophagy-related gene VPS13A and autophagy activation. These findings provide new insight into lncRNA-mediated mechanism for autophagy activation in NEPC and suggest PCAT-NE1 as a potential diagnostic biomarker and therapeutic target for NEPC. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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