ArticleNucleic acids research2019
Histone lysine demethylase KDM4B regulates the alternative splicing of the androgen receptor in response to androgen deprivation.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- The promising role of new molecular biomarkers in prostate cancer: from coding and non-coding genes to artificial intelligence approaches.Prostate cancer and prostatic diseases · 2022Pooled it
- Review
- RNA splicing in cancer cell death regulation: shedding light on the molecular mechanisms and potential clinical applications.Cell death & disease · 2026Review
- Androgen receptor splice variant 7 expression levels distinguish AR-mutated from nonmutated metastatic castration-resistant prostate cancers.The Journal of clinical investigation · 2026Article
- Genome Mining and Functional Characterization of Agarases from a Novel Vibrio Species.Marine biotechnology (New York, N.Y.) · 2026Article
- A novel spliceosomopathy caused by de novo SF3B3 variants.Genome medicine · 2026Article
- CoREST complex inhibition alters RNA splicing to promote neoantigen expression and enhance tumor immunity.JCI insight · 2026Article
- Regulation Ratio: A Singular Multi-Omic Measurement of Gene Regulatory Mechanisms.Computational and structural biotechnology journal · 2026Article
- Histone lysine demethylases in breast cancer: molecular mechanisms, biological functions, and therapeutic intervention.Molecular cancer · 2025Review
- KDM4B modulates ERα signaling pathway to participate in vascular smooth muscle cell calcification.Cell death discovery · 2025Article
- Endocrine cancer organoids in basic and translational medical research.Science China. Life sciences · 2025Review
- Prostate cancer epigenetics - from pathophysiology to clinical application.Nature reviews. Urology · 2025Review
- Review
- Histone-modifying enzymes as drivers and therapeutic targets in androgen-resistant prostate cancer.Frontiers in endocrinology · 2025Review
- Versatile JMJD proteins: juggling histones and much more.Trends in biochemical sciences · 2024Review
- The emerging roles of histone demethylases in cancers.Cancer metastasis reviews · 2024Review
- The Many Roads from Alternative Splicing to Cancer: Molecular Mechanisms Involving Driver Genes.Cancers · 2024Review
- Histone lysine demethylase 4 family proteins maintain the transcriptional program and adrenergic cellular state of MYCN-amplified neuroblastoma.Cell reports. Medicine · 2024Article
- Deubiquitinase USP7 stabilizes KDM5B and promotes tumor progression and cisplatin resistance in nasopharyngeal carcinoma through the ZBTB16/TOP2A axis.Cell death and differentiation · 2024Article
- Organoids: An Emerging Precision Medicine Model for Prostate Cancer Research.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
26 authors at 11 institutions in 2 countries.
Funding
Abstract
Alternative splicing is emerging as an oncogenic mechanism. In prostate cancer, generation of constitutively active forms of androgen receptor (AR) variants including AR-V7 plays an important role in progression of castration-resistant prostate cancer (CRPC). AR-V7 is generated by alternative splicing that results in inclusion of cryptic exon CE3 and translation of truncated AR protein that lacks the ligand binding domain. Whether AR-V7 can be a driver for CRPC remains controversial as the oncogenic mechanism of AR-V7 activation remains elusive. Here, we found that KDM4B promotes AR-V7 and identified a novel regulatory mechanism. KDM4B is phosphorylated by protein kinase A under conditions that promote castration-resistance, eliciting its binding to the splicing factor SF3B3. KDM4B binds RNA specifically near the 5'-CE3, upregulates the chromatin accessibility, and couples the spliceosome to the chromatin. Our data suggest that KDM4B can function as a signal responsive trans-acting splicing factor and scaffold that recruits and stabilizes the spliceosome near the alternative exon, thus promoting its inclusion. Genome-wide profiling of KDM4B-regulated genes also identified additional alternative splicing events implicated in tumorigenesis. Our study defines KDM4B-regulated alternative splicing as a pivotal mechanism for generating AR-V7 and a contributing factor for CRPC, providing insight for mechanistic targeting of CRPC.
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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.