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

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.