MYT1 attenuates neuroblastoma cell differentiation by interacting with the LSD1/CoREST complex.
Oncogene
; 39(21): 4212-4226, 2020 05.
Article
en En
| MEDLINE
| ID: mdl-32251364
ABSTRACT
Impaired neuronal differentiation is a feature of neuroblastoma tumorigenesis, and the differentiation grade of neuroblastoma tumors is associated with patient prognosis. Detailed understanding of the molecular mechanisms underlying neuroblastoma differentiation will facilitate the development of effective treatment strategies. Recent studies have shown that myelin transcription factor 1 (MYT1) promotes vertebrate neurogenesis by regulating gene expression. We performed quantitative analysis of neuroblastoma samples, which revealed that MYT1 was differentially expressed among neuroblastoma patients with different pathological diagnoses. Analysis of clinical data showed that MYT1 overexpression was associated with a significantly shorter 3-year overall survival rate and poor differentiation in neuroblastoma specimens. MYT1 knockdown inhibited proliferation and promoted the expression of multiple differentiation-associated proteins. Integrated omics data indicated that many genes involved in neuro-differentiation were regulated by MYT1. Interestingly, many of these genes are targets of the REST complex; therefore, we further identified the physical interaction of MYT1 with LSD1/CoREST. Depletion of LSD1 or inhibition of LSD1 by ORY-1001 decreased MYT1 expression, providing an alternative approach to target MYT1. Taken together, our results indicate that MYT1 significantly attenuates cell differentiation by interacting with the LSD1/CoREST complex. MYT1 is, therefore, a promising therapeutic target for enhancing the neurite-inducing effect of retinoic acid and for inhibiting the growth of neuroblastoma.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Diferenciación Celular
/
Complejos Multiproteicos
/
Proteínas de Unión al ADN
/
Histona Demetilasas
/
Proteínas Co-Represoras
/
Proteínas de Neoplasias
/
Proteínas del Tejido Nervioso
/
Neuroblastoma
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Female
/
Humans
/
Male
Idioma:
En
Revista:
Oncogene
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2020
Tipo del documento:
Article
País de afiliación:
China