ArticleCell death discovery2021
Dual EZH2 and G9a inhibition suppresses multiple myeloma cell proliferation by regulating the interferon signal and IRF4-MYC axis.
Article in Cell death discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed.
- Interferon regulatory factors orchestrate CD8International journal of molecular medicine · 2026Review
- The Trajectory of Epigenetic Chromatin Remodeling in Cardiometabolic Disease and its Therapeutic Implications.Journal of cardiovascular translational research · 2026Review
- EZH2 inhibition overcomes immunomodulatory drug resistance in multiple myeloma via a cereblon-dependent pathway.Haematologica · 2026Article
- Multiple myeloma: A tale of deregulated transcription factors.HemaSphere · 2026Review
- The nutrigenomic-epigenetic axis in cancer: from dietary bioactives to precision oncology.Nutrition & metabolism · 2026Review
- Endogenous protein tagging coupled with a CRISPR screening approach identifies UBE3C as a potential MYC oncogene regulator.Scientific reports · 2026Article
- PRC2 loss impairs small cell lung cancer tumorigenesis and enhances sensitivity to G9a/GLP inhibition.Communications biology · 2026Article
- Epigenetic regulation of EZH2 by ncRNAs: mechanisms and oncogenic implications.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Overcoming immunotherapy barriers in pediatric brain tumors: epigenetic strategies.Frontiers in oncology · 2026Review
- Activation of endogenous retroviruses in tumor cells and their immunomodulatory mechanisms: from molecular basis to clinical translation.Frontiers in oncology · 2026Review
- Endogenous retroviruses and response to immune checkpoint inhibitors: mechanisms, clinical evidence, and therapeutic implications.Frontiers in immunology · 2026Review
- DOT1L inhibition exerts the anti-tumor effect by activating interferon signaling in breast cancer cells.Clinical epigenetics · 2025Article
- Dual targeting of G9a and DNMTs induces antitumor effects in multiple myeloma.Blood advances · 2025Article
- UNC0638 inhibits SARS-CoV-2 entry by blocking cathepsin L maturation.Journal of virology · 2025Article
- G9a an Epigenetic Therapeutic Strategy for Neurodegenerative Conditions: From Target Discovery to Clinical Trials.Medicinal research reviews · 2025Review
- Short-term and long-term high-fat diet promote metabolic disorder through reprogramming mRNA mMicrobiome · 2025Article
- EZH2 serves as a viable therapeutic target for myeloma-induced osteolytic bone destruction.Nature communications · 2025Article
- Stage-specific gene pair ratios highlight genes and mechanisms related to presymptomatic and symptomatic Multiple Myeloma.Computational and structural biotechnology journal · 2025Article
- AEBP1 is a negative regulator of skeletal muscle cell differentiation in oral squamous cell carcinoma.Scientific reports · 2024Article
- Combining EHMT and PARP Inhibition: A Strategy to Diminish Therapy-Resistant Ovarian Cancer Tumor Growth while Stimulating Immune Activation.Molecular cancer therapeutics · 2024Article
Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epigenetic mechanisms such as histone modification play key roles in the pathogenesis of multiple myeloma (MM). We previously showed that EZH2, a histone H3 lysine 27 (H3K27) methyltransferase, and G9, a H3K9 methyltransferase, are potential therapeutic targets in MM. Moreover, recent studies suggest EZH2 and G9a cooperate to regulate gene expression. We therefore evaluated the antitumor effect of dual EZH2 and G9a inhibition in MM. A combination of an EZH2 inhibitor and a G9a inhibitor strongly suppressed MM cell proliferation in vitro by inducing cell cycle arrest and apoptosis. Dual EZH2/G9a inhibition also suppressed xenograft formation by MM cells in vivo. In datasets from the Gene Expression Omnibus, higher EZH2 and EHMT2 (encoding G9a) expression was significantly associated with poorer prognoses in MM patients. Microarray analysis revealed that EZH2/G9a inhibition significantly upregulated interferon (IFN)-stimulated genes and suppressed IRF4-MYC axis genes in MM cells. Notably, dual EZH2/G9a inhibition reduced H3K27/H3K9 methylation levels in MM cells and increased expression of endogenous retrovirus (ERV) genes, which suggests that activation of ERV genes may induce the IFN response. These results suggest that dual targeting of EZH2 and G9a may be an effective therapeutic strategy for MM.
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Registered trials
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