Department of Pediatrics, Peking University First Hospital, No. 1 Xi'an Men Street, West District, Beijing, 100034, China.
Beijing Key Laboratory of Molecular Diagnosis and Study on Pediatric Genetic Diseases, Beijing, China.
Neurochem Res. 2022 Dec;47(12):3723-3732. doi: 10.1007/s11064-022-03730-w. Epub 2022 Sep 6.
Neuroblastoma is a type of developmental childhood cancer that arises from the neural crest. It is the most common pediatric solid tumor in the world. AM580 is a powerful cyto-differentiating molecule on acute promyelocytic leukemia cells and induced pluripotent stem cells, but its effect on neuroblastoma is still unknown. In this study, the neuronal differentiation impact of AM580 was investigated using the human neuroblastoma cell line SH-SY5Y as a model. AM580 successfully stimulated the SH-SY5Y cells to develop into neuron-like cells. Functional enrichment analysis of RNAseq data revealed that differentially expressed genes (DEGs) were substantially enriched for GO keywords and KEGG pathways linked to neuron development. Some potassium ion channel genes associated with neuronal excitation, such as KCNT1, were shown to be upregulated. Through the MEA tests, we found the AM580-induced neurons possessed electrical spikes as mature neurons. AM580 also induced the neuronal marker β-tubulin III and mature neurons marker Neurofilament H. Our study proved that AM580 can promote the differentiation of neurons and has the potential to treat neuroblastoma, neurodevelopmental and neurodegenerative diseases.
神经母细胞瘤是一种起源于神经嵴的发育性儿童癌症。它是世界上最常见的小儿实体瘤。AM580 是急性早幼粒细胞白血病细胞和诱导多能干细胞上一种强大的细胞分化分子,但它对神经母细胞瘤的作用尚不清楚。在这项研究中,使用人神经母细胞瘤细胞系 SH-SY5Y 作为模型,研究了 AM580 对神经母细胞瘤的神经元分化影响。AM580 成功地刺激 SH-SY5Y 细胞分化为神经元样细胞。RNAseq 数据的功能富集分析表明,差异表达基因(DEGs)显著富集了与神经元发育相关的 GO 关键词和 KEGG 途径。一些与神经元兴奋相关的钾离子通道基因,如 KCNT1,被证明上调。通过 MEA 测试,我们发现 AM580 诱导的神经元具有成熟神经元的电脉冲。AM580 还诱导神经元标记物 β-微管蛋白 III 和成熟神经元标记物神经丝 H。我们的研究证明 AM580 可以促进神经元的分化,并有可能治疗神经母细胞瘤、神经发育和神经退行性疾病。