DNMT3B promotes neuroblastoma growth and survival, and its inhibition demonstrates antitumor effects.

ABSTRACT: Neuroblastoma is one of the most common childhood tumors and the current 5-year overall survival rate for children diagnosed at an advanced stage is less than 50%. Since tumor suppressor genes are often silenced via hypermethylation of promoter regions in tumors, DNA methylation has emerged as an attracting target against cancers. Despite the therapeutic potential of DNA methylation against neuroblastoma, conventional inhibitors of DNA methyltransferases have been reported to exhibit inadequate therapeutic effects and intolerable toxicities. Therefore, another approach through to neuroblastoma therapy via DNA demethylation is required to address the demand for clinical applications. Here, we demonstrate that the inhibition of DNA methyltransferase 3B (DNMT3B) exerts anti-tumor effects by upregulating apoptosis-related genes and downregulating tumor progression. We found that RNAi-mediated inhibition of DNMT3B induces widespread DNA demethylation, leading to increased expression of apoptosis-related genes such as tumor protein p53, retinoblastoma 1, and upregulating cellular functions associated with apoptosis. Tumor progression was weakened in DNMT3B knockdown neuroblastoma cells in vitro and in vivo whereas was promoted in DNMT3B overexpression neuroblastoma cell lines. In addition, a DNMT3B inhibitor nanaomycin A exhibits anti-tumor effects with apoptosis and DNA demethylation of tumor cells in a neuroblastoma cell line derived mouse xenograft model. In conclusion, our findings support a key role for DNMT3B in a novel therapeutic strategy for neuroblastoma.

ORGANISM(S): Homo sapiens

PROVIDER: GSE281320 | GEO | 2026/09/01

REPOSITORIES: GEO