ArticleFrontiers in oncology2020
Overexpression of EZH2/NSD2 Histone Methyltransferase Axis Predicts Poor Prognosis and Accelerates Tumor Progression in Triple-Negative Breast Cancer.
Article in Frontiers in oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 37 citations in OpenAlex.
- Stage-dependent expression and nuclear localization of EZH2 in endometrial carcinogenesis: evidence from cell lines and human tissues.Journal of molecular histology · 2026Article
- Epigenetic regulation of EZH2 by ncRNAs: mechanisms and oncogenic implications.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- How histone modifications influence cellular radiosensitivity: Pharmaceutically targeting epigenetic regulators as a promising avenue to overcome radioresistance.Acta pharmaceutica Sinica. B · 2025Review
- NSD2 mediates NF-κB and matrix metalloproteinases to drive hepatocellular carcinoma malignant progression.Translational cancer research · 2025Article
- The RNA-binding protein LARP6 regulates the alternative splicing of related genes in MDA-MB-231 cells.Scientific reports · 2025Article
- DNA Methylation-Based Diagnosis and Treatment of Breast Cancer.Current cancer drug targets · 2025Review
- Novel dual-targeting inhibitors of NSD2 and HDAC2 for the treatment of liver cancer: structure-based virtual screening, molecular dynamics simulation, andJournal of enzyme inhibition and medicinal chemistry · 2024Article
- Dual-target EZH2 inhibitor: latest advances in medicinal chemistry.Future medicinal chemistry · 2024Review
- Drug Discovery Targeting Nuclear Receptor Binding SET Domain Protein 2 (NSD2).Journal of medicinal chemistry · 2023Review
- The Role of Histone Modification in DNA Replication-Coupled Nucleosome Assembly and Cancer.International journal of molecular sciences · 2023Review
- Deletion of mdig enhances H3K36me3 and metastatic potential of the triple negative breast cancer cells.iScience · 2022Article
- High EZH2 Protein Expression Is a Poor Prognostic Predictor in IDH1 R132H-Negative Gliomas.Diagnostics (Basel, Switzerland) · 2022Article
- Clinicopathological Analysis of Expression of Enhancer of Zeste Homologue 2 in Canine Mammary Carcinoma.Journal of veterinary research · 2022Article
- Polyploid giant cancer cells, EZH2 and Myc upregulation in mammary epithelial cells infected with high-risk human cytomegalovirus.EBioMedicine · 2022Article
- Structural and functional specificity of H3K36 methylation.Epigenetics & chromatin · 2022Review
- Article
- The Roles of DNA Demethylases in Triple-Negative Breast Cancer.Pharmaceuticals (Basel, Switzerland) · 2021Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Two histone methyltransferases, enhancer of zeste homolog 2 (EZH2) and nuclear SET domain-containing 2 (NSD2), are aberrantly expressed in several types of human cancers. However, the regulatory relationship between EZH2 and NSD2 and their prognostic values in breast cancer (BC) have not been fully elucidated. In this study, we demonstrated that EZH2 and NSD2 were overexpressed in BC compared with benign lesions and normal tissues using tissue microarray, immunohistochemistry, and bioinformatic databases. Both EZH2 and NSD2 expression were associated with pathological grade of tumor and lymph node metastasis. A comprehensive survival analysis using Kaplan-Meier Plotter database indicated that EZH2 expression was negatively correlated with relapse-free survival (RFS), overall survival (OS), distant metastasis-free survival (DMFS), and postprogression survival (PPS) in 3951 BC patients, and NSD2 expression was negatively correlated with RFS and DMFS. Notably, EZH2 and NSD2 expression were coordinately higher in triple-negative breast cancer (TNBC) than that in other subtypes. Stable knockdown of EZH2 using lentiviral shRNA vector significantly reduced the proliferation, migration and invasion abilities of TNBC cell line MDA-MB-231 and MDA-MB-468, and downregulated NSD2 expression as well as the levels of H3K27me3 and H3K36me2, two histone methylation markers catalyzed by EZH2 and NSD2, respectively. By contrast, overexpression of EZH2 using adenovirus vector displayed an inverse phenotype. Furthermore, knockdown of NSD2 in EZH2-overexpressing cells could dramatically attenuate EZH2-mediated oncogenic effects. Bioinformatic analysis further revealed the function and pathway enrichments of co-expressed genes and interactive genes of EZH2/NSD2 axis, suggesting that EZH2/NSD2 axis was associated with cell division, mitotic nuclear division and transition of mitotic cell cycle in TNBC. Taken together, EZH2/NSD2 axis may act as a predictive marker for poor prognosis and accelerate the progression of TNBC.
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