Mitochondrial uncoupler and retinoic acid synergistically induce differentiation and inhibit proliferation in neuroblastoma.
Haowen JiangSarah Jane TicheClifford JiaJun HeMohamed JedouiBalint ForgoMeng ZhaoBo HeYang LiAlbert M LiAnh T TruongJestine HoCathyrin SimmermakerYanan YangMeng-Ning ZhouZhen HuDaniel J CuthbertsonKatrin J SvenssonFlorette K HazardHiroyuki ShimadaBill ChiuJiangbin YePublished in: bioRxiv : the preprint server for biology (2024)
Neuroblastoma is a leading cause of death in childhood cancer cases. Unlike adult malignancies, which typically develop from aged cells through accumulated damage and mutagenesis, neuroblastoma originates from neural crest cells with disrupted differentiation. This distinct feature provides novel therapeutic opportunities beyond conventional cytotoxic methods. Previously, we reported that the mitochondrial uncoupler NEN (niclosamide ethanolamine) activated mitochondria respiration to reprogram the epigenome, promoting neuronal differentiation. In the current study, we further combine NEN with retinoic acid (RA) to promote neural differentiation both in vitro and in vivo . The treatment increased the expression of RA signaling and neuron differentiation-related genes, resulting in a global shift in the transcriptome towards a more favorable prognosis. Overall, these results suggest that the combination of a mitochondrial uncoupler and the differentiation agent RA is a promising therapeutic strategy for neuroblastoma.
Keyphrases
- oxidative stress
- induced apoptosis
- rheumatoid arthritis
- childhood cancer
- dna methylation
- gene expression
- disease activity
- crispr cas
- machine learning
- ankylosing spondylitis
- young adults
- systemic lupus erythematosus
- endoplasmic reticulum stress
- blood brain barrier
- deep learning
- idiopathic pulmonary fibrosis
- binding protein
- neural network
- smoking cessation