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- Title
Hypoxia-Inducible Factor-1α (HIF-1α) Inhibition Impairs Retinoic Acid-Induced Differentiation in SH-SY5Y Neuroblastoma Cells, Leading to Reduced Neurite Length and Diminished Gene Expression Related to Cell Differentiation.
- Authors
Brum, Pedro Ozorio; Viola, Guilherme Danielski; Saibro-Girardi, Carolina; Tiefensee-Ribeiro, Camila; Brum, Matheus Ozorio; Gasparotto, Juciano; Krolow, Rachel; Moreira, José Cláudio Fonseca; Gelain, Daniel Pens
- Abstract
Neuroblastoma is the most common extracranial solid tumour in childhood, originated from cells of the neural crest during the development of the Sympathetic Nervous System. Retinoids are vitamin-A derived differentiating agents utilised to avoid disease resurgence in high-risk neuroblastoma treatment. Several studies indicate that hypoxia—a common feature of the tumoural environment—is a key player in cell differentiation and proliferation. Hypoxia leads to the accumulation of the hypoxia-inducible factor-1α (HIF-1α). This work aims to investigate the effects of the selective inhibition of HIF-1α on the differentiation induced by retinoic acid in human neuroblastoma cells from the SH-SY5Y lineage to clarify its role in cell differentiation. Our results indicate that HIF-1α inhibition impairs RA-induced differentiation by reducing neuron-like phenotype and diminished immunolabeling and expression of differentiation markers. HIF1A is involved in Retinoic Acid (RA) induced differentiation in SH-SY5Y neuroblastoma cells. siRNA HIF1A gene silencing leads to a weaker response to RA, demonstrated by changes in the neuro-like phenotype and diminished expression of differentiation markers.
- Subjects
CELL differentiation; NEUROBLASTOMA; GENE expression; SYMPATHETIC nervous system; NEURAL crest
- Publication
Neurochemical Research, 2022, Vol 47, Issue 2, p409
- ISSN
0364-3190
- Publication type
Article
- DOI
10.1007/s11064-021-03454-3