SOXC Enhances NGN2-Mediated Reprogramming of Glioblastoma Cells Into Neuron-Like Cells by Modulating RhoA and RAC1/CDC42 Pathway Activity.
CNS Neurosci Ther
; 30(10): e70075, 2024 Oct.
Article
em En
| MEDLINE
| ID: mdl-39390804
ABSTRACT
BACKGROUND:
Glioblastoma represents the most frequently diagnosed malignant neoplasm within the central nervous system. Human glioblastoma cells can be phenotypically reprogrammed into neuron-like cells through the forced expression of NEUROG2 and SOXC factors. NEUROG2 serves as a pioneer factor, establishing an initial framework for this transformation. However, the specific role of SOXC factors has not been fully elucidated.METHODS:
In this study, we used ChIP-seq to determine the potential target gene of NGN2. RNA-seq has been used to evaluate the transcriptional change during NGN2-SOX11-mediated neuron reprogramming. Immunofluorescence was used to determine the neuron reprogramming efficacy and cell proliferation ability. ChIP-qPCR, Co-IP, and Western Blot were performed to investigate the mechanism.RESULTS:
Our findings reveal that SOXC factors, in contrast to their previously identified function as transcriptional activators, act as transcriptional repressors. They achieve this by recruiting TRIM28 to suppress the expression of ECT2, a RhoGEF. This suppression results in the differential regulation of RhoA, RAC1, and CDC42 activities throughout the reprogramming process. We further establish that small molecules targeting RhoA and its effectors can substitute for SOXC factors in facilitating the neuronal reprogramming of glioblastoma cells.CONCLUSION:
These results underscore the pivotal role of SOXC factors' transcriptional repression and illuminate one of their specific downstream targets.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Glioblastoma
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Proteína cdc42 de Ligação ao GTP
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Proteínas rac1 de Ligação ao GTP
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Proteína rhoA de Ligação ao GTP
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Fatores de Transcrição Hélice-Alça-Hélice Básicos
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Reprogramação Celular
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Fatores de Transcrição SOXC
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Proteínas do Tecido Nervoso
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Neurônios
Limite:
Humans
Idioma:
En
Revista:
CNS Neurosci Ther
/
CNS neurosc. ther. (Print)
/
CNS neuroscience & therapeutics (Print)
Assunto da revista:
NEUROLOGIA
/
TERAPEUTICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Reino Unido