ArticleCell death discovery2019
Targeting Wnt/EZH2/microRNA-708 signaling pathway inhibits neuroendocrine differentiation in prostate cancer.
Article in Cell death discovery, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 60 citations in OpenAlex.
- Clonal selection of pre-existing neuroendocrine component in prostate cancer during androgen receptor signaling inhibitor therapy: A case report.Urology case reports · 2026Article
- Circular RNAs: key regulators in cancer stem cell dynamics.Molecular genetics and genomics : MGG · 2026Review
- The Quartet of Core Oncogenic Drivers in Neuroendocrine Prostate Cancer: Multi-Omics Dataset Integration to Forge a Translational Link Between Biology and Precision Therapy.International journal of biological sciences · 2026Review
- Mechanisms of neuroendocrine differentiation in castration-resistant prostate cancer and advances in the treatment of neuroendocrine prostate cancer.Annals of medicine · 2025Review
- Widespread activation and critical role of EMT and stemness in the neuroendocrine differentiation of prostate cancer (Review).Oncology reports · 2025Review
- Review
- Suppression of TP Rat Pancreatic Acinar Cell Apoptosis by hucMSC-Ex Carrying hsa-miR-21-5p via PTEN/PI3K Regulation.Stem cells international · 2025Article
- New Insights into Potential Therapeutic Targets for Neuroendocrine Prostate Cancer: From Bench to Clinic.Research (Washington, D.C.) · 2025Review
- Structural Optimization of Isoquinoline Derivatives from Lycobetaine and Their Inhibitory Activity against Neuroendocrine Prostate Cancer Cells.Molecules (Basel, Switzerland) · 2024Article
- Computational drug discovery pipelines identify NAMPT as a therapeutic target in neuroendocrine prostate cancer.Clinical and translational science · 2024Article
- Tissue-Based Diagnostic Biomarkers of Aggressive Variant Prostate Cancer: A Narrative Review.Cancers · 2024Review
- Yin Yang 1 promotes the neuroendocrine differentiation of prostate cancer cells via the non-canonical WNT pathway (FYN/STAT3).Clinical and translational medicine · 2023Article
- Targeting Key Players of Neuroendocrine Differentiation in Prostate Cancer.International journal of molecular sciences · 2023Review
- Calcium signalling pathways in prostate cancer initiation and progression.Nature reviews. Urology · 2023Review
- Combating breast cancer progression through combination therapy with hypomethylating agent and glucocorticoid.iScience · 2023Article
- Prognostic Significance of Chromogranin A Expression in the Initial and Second Biopsies in Metastatic Prostate Cancer.Journal of clinical medicine · 2023Article
- circEZH2Cancer science · 2023Article
- Role of transcription factors and chromatin modifiers in driving lineage reprogramming in treatment-induced neuroendocrine prostate cancer.Frontiers in cell and developmental biology · 2023Review
- Lineage plasticity and treatment resistance in prostate cancer: the intersection of genetics, epigenetics, and evolution.Frontiers in endocrinology · 2023Review
- Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Prostate cancer (PC) castration resistance has been linked to the differentiation of PC luminal cells into hormone-refractory neuroendocrine (NE) cells. However, the molecular mechanisms controlling the emergence of lethal NE prostate cancer (NEPC) remain unclear. The present study aimed to investigate the mechanisms underlying the transition from prostate adenocarcinoma to NEPC. The microRNA miR-708 was involved in NE differentiation and was downregulated in NEPC cells and tumor specimens. miR-708 targeted Sestrin-3 to inhibit Forkhead Box O1 (FOXO1) phosphorylation, resulting in apoptosis of prostate adenocarcinoma cells and AKT-inactivated NEPC cells, the latter of which was consistent with the progression of tumor xenografts in mice under miR-708 treatment. In silico analysis of PC and NEPC tumor specimens suggested that the polycomb repressive complex subunit Enhancer of zeste homolog 2 (EZH2) was particularly overexpressed in NEPC. Notably, EZH2 bound to the miR-708 promoter and induced its silencing in NEPC. Inhibition of EZH2 prevented NE differentiation of PC cells. EZH2 expression was regulated by both Cyclin Dependent Kinase 1 (CDK1) and Wnt signaling. Silencing transcription factor 4 (TCF4), as a key protein in Wnt signaling, prevented NEPC formation. These results provide a molecular basis for the roles of miR-708 and EZH2 in NE differentiation in PC and highlight a new paradigm in NEPC formation and survival.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.