Aberrant EZHIP expression drives tumorigenesis in osteosarcoma.

ABSTRACT: Osteosarcomas (OS) are aggressive bone tumors known for their extensive structural variations and rare recurrent oncogenic driver mutations. In this study, we identify ectopic expression of the oncohistone-mimic EZHIP in 20% of patients across two independent OS cohorts. We demonstrate that reduced deposition of the repressive H3K27me3 mark correlates with poor histological response to neoadjuvant therapy, serving as a predictor of patient outcomes. Through gain- and loss-of-function experiments, we provide functional evidence of the oncogenic activity of EZHIP in enhancing the aggressive characteristics of OS both in vitro and in vivo. EZHIP-induced epigenetic reprogramming reactivates developmental pathways and impedes the differentiation of mesenchymal progenitors, pushing them towards

SUBMITTER: Jawhar W 

PROVIDER: S-EPMC12284272 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature