ArticleOncogene2015
Stable oncogenic silencing in vivo by programmable and targeted de novo DNA methylation in breast cancer.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 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
51 citing papers in PubMed, 92 citations in OpenAlex.
- Epigenetic editing approaches maturity: AI-driven precision design, delivery innovation, and the road to clinical translation.Clinical epigenetics · 2026Review
- Recent Advances in Searching for DNMT Inhibitors and Their Potential Application in Treating Human Diseases.International journal of molecular sciences · 2026Review
- Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026Review
- Integration of CRISPR/dCas9-Based methylation editing with guide positioning sequencing identifies dynamic changes of mrDEGs in breast cancer progression.Cellular and molecular life sciences : CMLS · 2025Article
- The Promise of Epigenetic Editing for Treating Brain Disorders.Sub-cellular biochemistry · 2025Review
- The Role of DNMT Methyltransferases and TET Dioxygenases in the Maintenance of the DNA Methylation Level.Biomolecules · 2024Review
- SOX on tumors, a comfort or a constraint?Cell death discovery · 2024Review
- Neuroepigenetic Editing.Methods in molecular biology (Clifton, N.J.) · 2024Review
- Designing Epigenome Editors: Considerations of Biochemical and Locus Specificities.Methods in molecular biology (Clifton, N.J.) · 2024Article
- The chromatin architectural regulator SND1 mediates metastasis in triple-negative breast cancer by promoting CDH1 gene methylation.Breast cancer research : BCR · 2023Article
- Synthetic Epigenetic Reprogramming of Mesenchymal to Epithelial States Using the CRISPR/dCas9 Platform in Triple Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Functional Validation of the Putative Oncogenic Activity ofBiomedicines · 2022Article
- Enzyme-free targeted DNA demethylation using CRISPR-dCas9-based steric hindrance to identify DNA methylation marks causal to altered gene expression.Nature protocols · 2022Review
- CRISPR Technology in Cancer Diagnosis and Treatment: Opportunities and Challenges.Biochemical genetics · 2022Review
- Large-scale manipulation of promoter DNA methylation reveals context-specific transcriptional responses and stability.Genome biology · 2022Article
- Epigenetic Editing in Prostate Cancer: Challenges and Opportunities.Epigenetics · 2022Review
- Review
- DNMT3A and DNMT3B in Breast Tumorigenesis and Potential Therapy.Frontiers in cell and developmental biology · 2022Review
- Gene-Targeted DNA Methylation: Towards Long-Lasting Reprogramming of Gene Expression?Advances in experimental medicine and biology · 2022Review
- The high methylation level of a novel 151-bp CpG island in the ESR1 gene promoter is associated with a poor breast cancer prognosis.Cancer cell international · 2021Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
With the recent comprehensive mapping of cancer genomes, there is now a need for functional approaches to edit the aberrant epigenetic state of key cancer drivers to reprogram the epi-pathology of the disease. In this study we utilized a programmable DNA-binding methyltransferase to induce targeted incorporation of DNA methylation (DNAme) in the SOX2 oncogene in breast cancer through a six zinc finger (ZF) protein linked to DNA methyltransferase 3A (ZF-DNMT3A). We demonstrated long-lasting oncogenic repression, which was maintained even after suppression of ZF-DNMT3A expression in tumor cells. The de novo DNAme was faithfully propagated and maintained through cell generations even after the suppression of the expression of the chimeric methyltransferase in the tumor cells. Xenograft studies in NUDE mice demonstrated stable SOX2 repression and long-term breast tumor growth inhibition, which lasted for >100 days post implantation of the tumor cells in mice. This was accompanied with a faithful maintenance of DNAme in the breast cancer implants. In contrast, downregulation of SOX2 by ZF domains engineered with the Krueppel-associated box repressor domain resulted in a transient and reversible suppression of oncogenic gene expression. Our results indicated that targeted de novo DNAme of the SOX2 oncogenic promoter was sufficient to induce long-lasting epigenetic silencing, which was not only maintained during cell division but also significantly delayed the tumorigenic phenotype of cancer cells in vivo, even in the absence of treatment. Here, we outline a genome-based targeting approach to long-lasting tumor growth inhibition with potential applicability to many other oncogenic drivers that are currently refractory to drug design.
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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.