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

• Autor(a) principal: Brum, Pedro Ozorio
• Data de Publicação: 2022
• Outros Autores: Viola, Guilherme Danielski, Girardi, Carolina Saibro, Ribeiro, Camila Tiefensee, Brum, Matheus Ozorio, Gasparotto, Juciano, Krolow, Rachel, Moreira, Jose Claudio Fonseca, Gelain, Daniel Pens
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFRGS
• Texto Completo: http://hdl.handle.net/10183/238322
• topic: Neuroblastoma; Subunidade alfa do Fator 1 Induzível por Hipóxia; Tretinoína; Diferenciação celular; Células tumorais cultivadas; Hypoxia; Differentiation; Neuroblastoma; Cancer; HIF-1; SH-SY5Y

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.