Epigenetic silencing of ZIC4 unveils a potential tumor suppressor role in pediatric choroid plexus carcinoma.
Sci Rep
; 14(1): 21293, 2024 09 12.
Article
em En
| MEDLINE
| ID: mdl-39266576
ABSTRACT
Zic family member ZIC4 is a transcription factor that has been shown to be silenced in several cancers. However, understanding the regulation and function of ZIC4 in pediatric choroid plexus tumors (CPTs) remained limited. This study employed data mining and bioinformatics analysis to investigate the DNA methylation status of ZIC4 in CPTs and its correlation with patient survival. Our results unveiled ZIC4 methylation as a segregating factor, dividing CPT cohorts into two clusters, with hyper-methylation linked to adverse prognosis. Hyper-methylation of ZIC4 was confirmed in a choroid plexus carcinoma-derived cell line (CCHE-45) by bisulfite sequencing. Furthermore, our study demonstrated that demethylating agent and a histone methyltransferase inhibitor could reverse ZIC4 silencing. RNA sequencing and proteomic analysis showed that ZIC4 over-expression influenced genes and proteins involved in immune response, antigen processing and presentation, endoplasmic reticulum stress, and metabolism. Functionally, re-expressing ZIC4 negatively impacted cell proliferation and migration. Ultimately, these findings underscore ZIC4 hyper-methylation as a prognostic marker in CPTs and shed light on potential mechanisms underlying its tumor suppressor role in CPC. This insight paves the way for novel therapeutic targets in treating aggressive CPTs.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Regulação Neoplásica da Expressão Gênica
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Neoplasias do Plexo Corióideo
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Metilação de DNA
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Epigênese Genética
Limite:
Child
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Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2024
Tipo de documento:
Article