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Background <p>Neuroblastoma is one of the most common childhood tumors. As tumor suppressor genes are frequently silenced <i>via</i> 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.</p> Methods <p>DNMT3B 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.</p> Results <p>DNMT3B 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.</p> Conclusion <p>This 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.</p> Impact <p><UnorderedList Mark="Bullet"> <ItemContent> <p>We propose selective inhibition of DNMT3B as a new approach in neuroblastoma treatment.</p> </ItemContent> <ItemContent> <p>DNMT3B enhanced disease progression in neuroblastoma cell lines and a cell line–derived xenograft model.</p> </ItemContent> <ItemContent> <p>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.</p> </ItemContent> </UnorderedList></p>

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Neuroblastoma cell growth and survival promoted by DNMT3B and its inhibition demonstrates anti-tumor effects

  • 期刊论文

  • 发表日期：

    2026年4月30日

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  • Kazuya Izumi,
  • Hiromasa Aoki,
  • Kohki Toriuchi,
  • Chiharu Miyajima,
  • Takaomi Sanda,
  • Satoru Takeshita,
  • Hiroki Kakita,
  • Yasumichi Inoue,
  • Shinsuke Iida,
  • Yasumasa Yamada,
  • Mineyoshi Aoyama

摘要

Background

Neuroblastoma 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.

Methods

DNMT3B 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.

Results

DNMT3B 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.

Conclusion

This 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.