ArticlePediatric research2026
Neuroblastoma cell growth and survival promoted by DNMT3B and its inhibition demonstrates anti-tumor effects.
Article in Pediatric research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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11 authors.
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Abstract
backgroundNeuroblastoma is one of the most common childhood tumors. As tumor suppressor genes are frequently silenced via promoter hypermethylation in cancers, targeting DNA methylation has become a promising therapeutic approach. Despite the therapeutic potential of targeting DNA methylation in neuroblastoma, conventional inhibitors of DNA methyltransferases (DNMTs) reportedly exhibit inadequate therapeutic efficacy and intolerable toxicity. Therefore, a more selective approach targeting DNA methylation enzymes that contribute to neuroblastoma progression is warranted.
methodsDNMT3B expression in neuroblastoma patients was analyzed using public microarray data. The role of DNMT3B in neuroblastoma was assessed using neuroblastoma cell lines and a cell line-derived neuroblastoma xenograft model. Gene expression changes induced by DNMT3B knockdown in neuroblastoma cells were comprehensively analyzed using RNA sequencing.
resultsDNMT3B expression was higher in advanced neuroblastoma patients and correlated with poor prognosis. DNMT3B knockdown induced DNA demethylation, leading to enhanced apoptosis-related gene expression and cellular functions. Tumor progression was weakened by DNMT3B knockdown both in vitro and in vivo. The DNMT3B inhibitor nanaomycin A showed anti-tumor effects in a neuroblastoma xenograft model.
conclusionThis study revealed the tumor-promoting role of DNMT3B in neuroblastoma through in vitro analyses and provided in vivo evidence that DNMT3B inhibition suppresses tumor growth. IMPACT: We propose selective inhibition of DNMT3B as a new approach in neuroblastoma treatment. DNMT3B enhanced disease progression in neuroblastoma cell lines and a cell line-derived xenograft model. Nanaomycin A, a small-molecule inhibitor of DNMT3B, exhibited significant anti-tumor effects on neuroblastoma in vivo, supporting the potential for targeting DNMT3B in neuroblastoma treatment.
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