Epigenetic Inactivation of RIPK3-Dependent Necroptosis Augments Cisplatin Chemoresistance in Human Osteosarcoma.

ABSTRACT: Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents. Unfortunately, drug resistance limits the efficacy of chemotherapeutic treatment and compromises therapeutic outcomes in a substantial proportion of cases. Aberrant CpG island methylation-associated transcriptional silencing contributes to chemoresistance in pediatric solid tumors. Here, using whole-genome DNA methylation screening on 16 human primary OS specimens, we identify receptor interacting protein kinase-3 (RIPK3), a molecular regulator of the necroptosis programmed cell death pathway, as a gene target of aberrant CpG methylation and demonstrate its role in human OS chemoresistance. We validated these findings via enforced expression and DsiRNA silencing, and evaluated the role of RIPK3 in cis

SUBMITTER: Sharma A 

PROVIDER: S-EPMC12027565 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature