Abstract 2099: N-Myc-mediated epigenetic reprogramming drives lineage plasticity in advanced prostate cancer

Berger, Adeline; Brady, Nicholas J.; Bareja, Rohan; Robinson, Brian; Conteduca, Vincenza; Augello, Michael A.; Puca, Loredana; Ahmed, Adnan; Lü, Xiaodong; Hwang, Inah; Bagadion, Alyssa; Sboner, Andrea; Elemento, Olivier; Paik, Jihye; Yu, Jindan; Barbieri, Christopher E.; Dephoure, Noah; Beltran, Himisha; Rickman, David S.

doi:10.1158/1538-7445.sabcs18-2099

Cited by 2 publications

(1 citation statement)

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“…One of the most striking observations was that NEPC minimizes AR dependency coinciding with the acquisition of a NE phenotype. In addition to gene mutations and ampli cations [37][38][39][40][41][42], epigenetic regulation of chromatin accessibility for transcription was also found to play a key role in NEPC [18, [43][44][45]. More importantly, the epigenetic/non-coding interactome is emerging as a novel mechanism that orchestrates the initiation and progression of NEPC [26, 28].…”

Section: Discussionmentioning

confidence: 99%

A novel REST-regulated lncRNA PCAT-NE1 induces neuroendocrine differentiation in castration-resistant prostate cancer

Chang

Yeh

Cheng

et al. 2022

Preprint

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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.

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Section: Discussionmentioning

confidence: 99%

A novel REST-regulated lncRNA PCAT-NE1 induces neuroendocrine differentiation in castration-resistant prostate cancer

Chang

Yeh

Cheng

et al. 2022

Preprint

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Single-cell analysis supports a luminal-neuroendocrine trans-differentiation in human prostate cancer

Dong

Miao

Wang

et al. 2020

Preprint

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Neuroendocrine prostate cancer is one of the most aggressive subtypes of prostate tumor. Although much progress has been made in understanding the development of neuroendocrine prostate cancer, the cellular architecture associated with neuroendocrine differentiation in human prostate cancer remain incompletely understood. Here, we use single-cell RNA sequencing to profile the transcriptomes of 21,292 cells from needle biopsies of 6 castration-resistant prostate cancers. Our analyses reveal that all neuroendocrine tumor cells display a luminal-like epithelial phenotype. In particular, lineage trajectory analysis suggests that focal neuroendocrine differentiation exclusively originate from luminal-like malignant cells rather than basal compartment. Further tissue microarray analysis validates the generality of the luminal phenotype of neuroendocrine cells. Moreover, we uncover neuroendocrine differentiation-associated gene signatures that may help us to further explore novel intrinsic molecular mechanisms deriving neuroendocrine prostate cancer.In summary, our single-cell study provides direct evidence into the cellular states underlying neuroendocrine transdifferentiation in human prostate cancer.

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Abstract 2099: N-Myc-mediated epigenetic reprogramming drives lineage plasticity in advanced prostate cancer

Cited by 2 publications

References 0 publications

A novel REST-regulated lncRNA PCAT-NE1 induces neuroendocrine differentiation in castration-resistant prostate cancer

A novel REST-regulated lncRNA PCAT-NE1 induces neuroendocrine differentiation in castration-resistant prostate cancer

Single-cell analysis supports a luminal-neuroendocrine trans-differentiation in human prostate cancer

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