ArticleNature communications2025
EZH2 serves as a viable therapeutic target for myeloma-induced osteolytic bone destruction.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Structural characteristics and SARs of EZH2 inhibitors.Molecular diversity · 2026Review
- SEI1 complex silences p53 to drive myeloma progression.iScience · 2026Article
- Deciphering epigenetic crosstalk in multiple myeloma pathogenesis and treatment.Clinical epigenetics · 2026Review
- Endothelial-specific Ezh2 deficiency exacerbates blood-brain barrier dysfunction and neuroinflammation in sepsis-associated encephalopathy.Journal of neuroinflammation · 2026Article
- UTX Responds to Nanotopography to Suppress Macrophage Inflammatory Response by Remodeling H3K27me3 Modification.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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Authors and funding
6 authors.
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Abstract
Myelomatous bone disease is a complication characterized by lytic bone lesions, reduced bone formation, bone pain, and increased fracture risk. Understanding these underlying mechanisms is crucial for developing effective therapeutic approaches. Here we show the role of enhancer of zeste homolog 2 (EZH2) in bone lesions induced by myeloma cells. Our research reveals that cytokines produced by myeloma-associated adipocytes activate the expression of EZH2 in myeloma cells. Furthermore, we find that EZH2 forms a transcriptional repression complex with transcription factor AP2α. This complex promotes trimethylation at lysine 27 of histone H3 (H3K27me3) in the promoter region of the tumor suppressor gene EMP1, resulting in transcriptional silencing. EMP1 silencing leads to increased myeloma cell proliferation and the concomitant secretion of osteolytic cytokines that contribute to bone destruction. Importantly, EZH2 inhibitors effectively treat myeloma-induced osteolytic lesions. Thus, targeting EZH2 represents a potential therapeutic strategy for preventing and managing myeloma bone disease.
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