Integrative analysis of genomic and epigenomic regulation reveals miRNA mediated tumor heterogeneity and immune evasion in lower grade glioma.
Commun Biol
; 7(1): 824, 2024 Jul 06.
Article
em En
| MEDLINE
| ID: mdl-38971948
ABSTRACT
The expression dysregulation of microRNAs (miRNA) has been widely reported during cancer development, however, the underling mechanism remains largely unanswered. In the present work, we performed a systematic integrative study for genome-wide DNA methylation, copy number variation and miRNA expression data to identify mechanisms underlying miRNA dysregulation in lower grade glioma. We identify 719 miRNAs whose expression was associated with alterations of copy number variation or promoter methylation. Integrative multi-omics analysis revealed four subtypes with differing prognoses. These glioma subtypes exhibited distinct immune-related characteristics as well as clinical and genetic features. By construction of a miRNA regulatory network, we identified candidate miRNAs associated with immune evasion and response to immunotherapy. Finally, eight prognosis related miRNAs were validated to promote cell migration, invasion and proliferation through in vitro experiments. Our study reveals the crosstalk among DNA methylation, copy number variation and miRNA expression for immune regulation in glioma, and could have important implications for patient stratification and development of biomarkers for immunotherapy approaches.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Encefálicas
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Regulação Neoplásica da Expressão Gênica
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Metilação de DNA
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MicroRNAs
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Variações do Número de Cópias de DNA
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Glioma
Limite:
Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article