Journal
NEUROCHEMICAL RESEARCH
Volume 47, Issue 12, Pages 3723-3732Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11064-022-03730-w
Keywords
AM580; SH-SY5Y cell; Neuronal differentiation; Mature neuron; RNAseq
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Funding
- National Key Research and Development Program of China [2020YFA0804000]
- National Natural Science Foundation of China [82171435, 81971211, 81601131]
- Key Project of Clinical Medicine Research of National Clinical Research Center for Child Health and Disorders, Children's Hospital of Chongqing Medical University [NCRCCHD-2021-KP-02]
- Beijing Natural Science Foundation [7212109]
- Beijing Key Laboratory of Molecular Diagnosis and Study on Pediatric Genetic Diseases [BZ0317]
- Fundamental Research Funds for the Central Universities [BMU2017JI002, PKU2017LCX06]
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Our study demonstrated the potential of AM580 to promote neuronal differentiation and treat neuroblastoma, neurodevelopmental, and neurodegenerative diseases.
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 beta-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.
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