ArticleNature communications2020
Histone methyltransferase DOT1L coordinates AR and MYC stability in prostate cancer.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
72 citing papers in PubMed, 109 citations in OpenAlex.
- Review
- Targeting DOT1L Reactivates HERV-K to Drive Cell-Autonomous and Paracrine Senescence in Adenocarcinoma of the Esophagogastric Junction.Cancer research · 2026Article
- Anti-tumor Effects of Pollen Pini on Hepatocarcinoma SMMC-7721 Cells via Modulation of PI3K-Akt Signaling Pathway.Chinese journal of integrative medicine · 2026Article
- KDM4A promotes NEPC progression through regulation of MYC expression.Cancer letters · 2026Article
- Lineage-determining transcription factors constrain cohesin to drive multi-enhancer oncogene regulation.Nature cell biology · 2026Article
- DOT1L promotes immune evasion in lung adenocarcinoma through H3K79me2-mediated epigenetic activation of immune checkpoints.Frontiers in immunology · 2026Article
- DOT1L inhibition exerts the anti-tumor effect by activating interferon signaling in breast cancer cells.Clinical epigenetics · 2025Article
- ERG-driven prostate cancer initiation is cell-context dependent and requires KMT2A and DOT1L.Nature genetics · 2025Article
- MODA: a graph convolutional network-based multi-omics integration framework for unraveling hub molecules and disease mechanisms.Briefings in bioinformatics · 2025Article
- Leveraging sequences missing from the human genome to diagnose cancer.Communications medicine · 2025Article
- Review
- H3K79 methylation and H3K36 trimethylation synergistically regulate gene expression in pluripotent stem cells.Science advances · 2025Article
- Prostate cancer epigenetics - from pathophysiology to clinical application.Nature reviews. Urology · 2025Review
- Design, synthesis and evaluation of pyrimidinobenzylamide and pyrimidinothiophenamide derivatives as inhibitors of DOT1L and related epigenetic targets DNMT3a, PRMT4 and other HMTs.RSC medicinal chemistry · 2025Article
- PIM kinase inhibition counters resistance to radiotherapy and chemotherapy in human prostate cancer.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2025Article
- A CHD8-TRRAP axis facilitates MYC and E2F target gene regulation in human neural stem cells.iScience · 2025Article
- Exploring the Therapeutic Potential of the DOT1L Inhibitor EPZ004777 Using Bioinformatics and Molecular Docking Approaches in Acute Myeloid Leukemia.Current issues in molecular biology · 2025Article
- DOT1L Mediates Stem Cell Maintenance and Represents a Therapeutic Vulnerability in Cancer.Cancer research · 2025Review
- Challenges and opportunities for the diverse substrates of SPOP E3 ubiquitin ligase in cancer.Theranostics · 2025Review
- TET2 gene mutation status associated with poor prognosis of transition zone prostate cancer: a retrospective cohort study based on whole exome sequencing and machine learning models.Frontiers in endocrinology · 2025Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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- Commented on byUro-Science.2021
Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
The histone methyltransferase DOT1L methylates lysine 79 (K79) on histone H3 and is involved in Mixed Lineage Leukemia (MLL) fusion leukemogenesis; however, its role in prostate cancer (PCa) is undefined. Here we show that DOT1L is overexpressed in PCa and is associated with poor outcome. Genetic and chemical inhibition of DOT1L selectively impaired the viability of androgen receptor (AR)-positive PCa cells and organoids, including castration-resistant and enzalutamide-resistant cells. The sensitivity of AR-positive cells is due to a distal K79 methylation-marked enhancer in the MYC gene bound by AR and DOT1L not present in AR-negative cells. DOT1L inhibition leads to reduced MYC expression and upregulation of MYC-regulated E3 ubiquitin ligases HECTD4 and MYCBP2, which promote AR and MYC degradation. This leads to further repression of MYC in a negative feed forward manner. Thus DOT1L selectively regulates the tumorigenicity of AR-positive prostate cancer cells and is a promising therapeutic target for PCa.
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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.