ArticleNeoplasia (New York, N.Y.)2020
Alternative splicing of LSD1+8a in neuroendocrine prostate cancer is mediated by SRRM4.
Article in Neoplasia (New York, N.Y.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- Genetic and epigenetic mechanisms underlying treatment-induced neuroendocrine prostate cancer.Journal of the National Cancer Center · 2026Review
- New frontiers in prostate cancer treatment from systemic therapy to targeted therapy.EMBO molecular medicine · 2025Review
- New Insights into Potential Therapeutic Targets for Neuroendocrine Prostate Cancer: From Bench to Clinic.Research (Washington, D.C.) · 2025Review
- The emerging roles of histone demethylases in cancers.Cancer metastasis reviews · 2024Review
- Targeting Key Players of Neuroendocrine Differentiation in Prostate Cancer.International journal of molecular sciences · 2023Review
- The Oncogenic Protein Kinase/ATPase RIOK1 Is Up-Regulated via the c-myc/E2F Transcription Factor Axis in Prostate Cancer.The American journal of pathology · 2023Article
- An antisense amido-bridged nucleic acid gapmer oligonucleotide targeting SRRM4 alters REST splicing and exhibits anti-tumor effects in small cell lung cancer and prostate cancer cells.Cancer cell international · 2023Article
- Lineage plasticity and treatment resistance in prostate cancer: the intersection of genetics, epigenetics, and evolution.Frontiers in endocrinology · 2023Review
- Understanding Drug Sensitivity and Tackling Resistance in Cancer.Cancer research · 2022Article
- Aggressive variants of prostate cancer: underlying mechanisms of neuroendocrine transdifferentiation.Journal of experimental & clinical cancer research : CR · 2022Review
- RB1 loss in castration-resistant prostate cancer confers vulnerability to LSD1 inhibition.Oncogene · 2022Article
- Phenotypic Plasticity - Alternate Transcriptional Programs Driving Treatment Resistant Prostate Cancer.Critical reviews in oncogenesis · 2022Review
- The Role of Epigenetic Change in Therapy-Induced Neuroendocrine Prostate Cancer Lineage Plasticity.Frontiers in endocrinology · 2022Review
- Prostate cancer: Alternatively spliced mRNA transcripts in tumor progression and their uses as therapeutic targets.The international journal of biochemistry & cell biology · 2021Review
- RNA Splicing Factors SRRM3 and SRRM4 Distinguish Molecular Phenotypes of Castration-Resistant Neuroendocrine Prostate Cancer.Cancer research · 2021Article
- The heterogeneity of prostate cancers lacking AR activity will require diverse treatment approaches.Endocrine-related cancer · 2021Review
- Recent Advances in Epigenetic Biomarkers and Epigenetic Targeting in Prostate Cancer.European urology · 2021Review
- The emerging role of KDM5A in human cancer.Journal of hematology & oncology · 2021Review
- Dynamics of Cellular Plasticity in Prostate Cancer Progression.Frontiers in molecular biosciences · 2020Review
- Immunotherapeutic Significance of a Prognostic Alternative Splicing Signature in Bladder Cancer.Technology in cancer research & treatmentArticle
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
Neuroendocrine prostate cancer (NEPC) is the most virulent form of prostate cancer. Importantly, our recent work examining metastatic biopsy samples demonstrates NEPC is increasing in frequency. In contrast to prostate adenocarcinomas that express a luminal gene expression program, NEPC tumors express a neuronal gene expression program. Despite this distinction, the diagnosis of NEPC is often challenging, demonstrating an urgent need to identify new biomarkers and therapeutic targets. Our prior work demonstrated that the histone demethylase LSD1 (KDM1A) is important for survival of prostate adenocarcinomas, but little was known about LSD1's role in NEPC. Recently, a neural-specific transcript variant of LSD1-LSD1+8a-was discovered and demonstrated to activate neuronal gene expression in neural cells. The splicing factor SRRM4 was previously shown to promote LSD1+8a splicing in neuronal cells, and SRRM4 promotes NEPC differentiation and cell survival. Therefore, we sought to determine if LSD1+8a might play a role in NEPC and whether LSD1+8a splicing was linked to SRRM4. To investigate a potential role for LSD1+8a in NEPC, we examined a panel of prostate adenocarcinoma and NEPC patient-derived xenografts and metastatic biopsies. LSD1+8a was expressed exclusively in NEPC samples and correlated significantly with elevated expression of SRRM4. Using SRRM4-overexpressing cell lines, we determined that SRRM4 mediates alternative splicing of LSD1+8a. Finally, using gain of function studies, we confirmed that LSD1+8a and SRRM4 co-regulate target genes distinct from canonical LSD1. Our findings suggest further study of the interplay between SRRM4 and LSD1+8a and mechanisms by which LSD1+8a regulates gene expression in NEPC is warranted.
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What OpenQuestion holds
Registered trials
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.