ArticleSignal transduction and targeted therapy2022
The DNMT1-PAS1-PH20 axis drives breast cancer growth and metastasis.
Article in Signal transduction and targeted therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 106 citations in OpenAlex.
- Dynamic regulation of H3K9 modifications in cancer: pathogenesis and targeted therapies.Biomarker research · 2026Review
- Epigenetic Mechanisms in Sepsis-Induced Cardiomyopathy: From Pathophysiology to Therapeutic Targets.International journal of molecular sciences · 2026Review
- Single-cell transcriptome analysis reveals DNMT1Journal of translational medicine · 2026Article
- LncRNA TMPO-AS1 aggravates the cisplatin resistance in cervical cancer via miR-140-5p/DNMT1 axis-mediated DNA methylation of KLK10.Medical oncology (Northwood, London, England) · 2026Article
- The Great Potential of DNA Methylation in Triple-Negative Breast Cancer: From Biological Basics to Clinical Application.Biomedicines · 2026Review
- Subtype-Dependent Transcriptional Coupling Between DNMT1 and E2F-Linked Proliferative Programs in Breast Cancer: A Dual-Cohort Transcriptomic Analysis.Journal of Cancer · 2026Article
- DNMT1 modulation of RASSF1A methylation enhances breast cancer brain metastasis.Cell death & disease · 2025Article
- Targeting the redox-programmed cell death axis in breast cancer: from molecular mechanisms to therapeutic resistance.Cell death discovery · 2025Review
- Landscape analysis of m5C modification regulators unveils DNMT1-mediated dysregulated pyrimidine metabolism in hepatocellular carcinoma.Clinical epigenetics · 2025Article
- Necroptosis in cancer: insight from epigenetic, post-transcriptional and post-translational modifications.Journal of hematology & oncology · 2025Review
- Targeting epigenetic regulators as a promising avenue to overcome cancer therapy resistance.Signal transduction and targeted therapy · 2025Review
- LncRNA MIR503HG regulates NETs-mediated NLRP3 inflammasome activation and NSCLC metastasis by enhancing the ubiquitination of C/EBPβ.Clinical and translational medicine · 2025Article
- Hyaluronan: An Architect and Integrator for Cancer and Neural Diseases.International journal of molecular sciences · 2025Review
- A Comprehensive Review on LncRNAs/miRNAs-DNMT1 Axis in Human Cancer: Mechanistic and Clinical Application.Journal of cellular and molecular medicine · 2025Review
- The multiple functions and mechanisms of long non-coding RNAs in regulating breast cancer progression.Frontiers in pharmacology · 2025Review
- DNA Methylation-Based Diagnosis and Treatment of Breast Cancer.Current cancer drug targets · 2025Review
- Epigenetic crosstalk between stem cells and tumors: mechanisms and emerging perspectives.American journal of stem cells · 2025Review
- Mechanisms and cross-talk of regulated cell death and their epigenetic modifications in tumor progression.Molecular cancer · 2024Review
- Enhancing antitumor activity of herceptin in HER2-positive breast cancer cells: a novel DNMT-1 inhibitor approach.Discover oncology · 2024Article
- Mechanistic role of long non-coding RNAs in the pathogenesis of metabolic dysfunction-associated steatotic liver disease and fibrosis.eGastroenterology · 2024Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PH20 is a member of the human hyaluronidase family that degrades hyaluronan in the extracellular matrix and controls tumor progression. Inhibition of DNA methyltransferases (DNMTs) leads to elevated hyaluronan levels; however, whether DNMT inhibitors control PH20 remains unclear. Here, we report that the DNMT1 inhibitor, decitabine, suppresses PH20 expression by activating the long non-coding RNA PHACTR2-AS1 (PAS1). PAS1 forms a tripartite complex with the RNA-binding protein vigilin and histone methyltransferase SUV39H1. The interaction between PAS1 and vigilin maintains the stability of PAS1. Meanwhile, PAS1 recruits SUV39H1 to trigger the H3K9 methylation of PH20, resulting in its silencing. Functionally, PAS1 inhibits breast cancer growth and metastasis, at least partially, by suppressing PH20. Combination therapy of decitabine and PAS1-30nt-RNA, which directly binds to SUV39H1, effectively blocked breast cancer growth and metastasis in mice. Taken together, DNMT1, PAS1, and PH20 comprise a regulatory axis to control breast cancer growth and metastasis. These findings reveal that the DNMT1-PAS1-PH20 axis is a potential therapeutic target for breast cancer.
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