EZH2 serves as a viable therapeutic target for myeloma-induced osteolytic bone destruction

Rui Liu, Zongwei Li, Rui Chen, Zhihong Fang, Zhiqiang Liu () and Huan Liu ()
Additional contact information
Rui Liu: Xiamen University
Zongwei Li: Anhui Medical University
Rui Chen: Xiamen University
Zhihong Fang: Xiamen University
Zhiqiang Liu: Shandong First Medical University and Shandong Academy of Medical Sciences
Huan Liu: Xiamen University

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: 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.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-56506-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56506-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-56506-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().