2. Academic Validation
  3. Neuroblastoma SH-SY5Y Cell Differentiation to Mature Neuron by AM580 Treatment

Neuroblastoma SH-SY5Y Cell Differentiation to Mature Neuron by AM580 Treatment

  • Neurochem Res. 2022 Sep 6. doi: 10.1007/s11064-022-03730-w.
Aojie Cai  # 1 2 3,  Zehong Lin  # 4,  Nana Liu 1 2 3,  Xiao Li 1 2 3,  Jingmin Wang 1 2 3 4,  Ye Wu 1 2 3,  Kai Gao 5 6 7 8,  Yuwu Jiang 9 10 11 12 13
Affiliations

Affiliations

  • 1 Department of Pediatrics, Peking University First Hospital, No. 1 Xi'an Men Street, West District, Beijing, 100034, China.
  • 2 Beijing Key Laboratory of Molecular Diagnosis and Study on Pediatric Genetic Diseases, Beijing, China.
  • 3 Children Epilepsy Center, Peking University First Hospital, Beijing, China.
  • 4 Department of Neurology, Affiliated Children's Hospital of Capital Institute of Pediatrics, Beijing, 100020, China.
  • 5 Department of Pediatrics, Peking University First Hospital, No. 1 Xi'an Men Street, West District, Beijing, 100034, China. gaokai_glia@163.com.
  • 6 Beijing Key Laboratory of Molecular Diagnosis and Study on Pediatric Genetic Diseases, Beijing, China. gaokai_glia@163.com.
  • 7 Children Epilepsy Center, Peking University First Hospital, Beijing, China. gaokai_glia@163.com.
  • 8 Key Laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, China. gaokai_glia@163.com.
  • 9 Department of Pediatrics, Peking University First Hospital, No. 1 Xi'an Men Street, West District, Beijing, 100034, China. jiangyw@263.net.
  • 10 Beijing Key Laboratory of Molecular Diagnosis and Study on Pediatric Genetic Diseases, Beijing, China. jiangyw@263.net.
  • 11 Children Epilepsy Center, Peking University First Hospital, Beijing, China. jiangyw@263.net.
  • 12 Key Laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, China. jiangyw@263.net.
  • 13 Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing, China. jiangyw@263.net.
  • # Contributed equally.
PMID: 36066699 DOI: 10.1007/s11064-022-03730-w
Abstract

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.

Keywords

AM580; Mature neuron; Neuronal differentiation; RNAseq; SH-SY5Y cell.

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