Combinatorial epigenetic regulation of non-coding RNAs has profound effects on oncogenic pathways in breast cancer subtypes.
Brief Bioinform
; 19(1): 52-64, 2018 01 01.
Article
en En
| MEDLINE
| ID: mdl-27742663
ABSTRACT
Although systematic genomic studies have identified a broad spectrum of non-coding RNAs (ncRNAs) that are involved in breast cancer, our understanding of the epigenetic dysregulation of those ncRNAs remains limited. Here, we systematically analysed the epigenetic alterations of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in two breast cancer subtypes (luminal and basal). Widespread epigenetic alterations of miRNAs and lncRNAs were observed in both cancer subtypes. In contrast to protein-coding genes, the majority of epigenetically dysregulated ncRNAs were shared between subtypes, but a subset of transcriptomic and corresponding epigenetic changes occurred in a subtype-specific manner. In addition, our findings suggested that various types of epi-modifications might synergistically modulate ncRNA transcription. Our observations further highlighted the complementary dysregulation of epi-modifications, particularly of miRNA members within the same family, which produced the same directed alterations as a result of diverse epi-modifications. Functional enrichment analysis revealed that epigenetically dysregulated ncRNAs were significantly involved in several hallmarks of cancers. Finally, our analysis of epigenetic modification-mediated miRNA regulatory networks revealed that cancer progression was associated with specific miRNA-gene modules in two subtypes. This study enhances understanding of the aberrant epigenetic patterns of ncRNA expression and provides new insights into the functions of ncRNAs in breast cancer subtypes.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Biomarcadores de Tumor
/
Regulación Neoplásica de la Expresión Génica
/
ARN no Traducido
/
MicroARNs
/
Epigénesis Genética
/
Carcinogénesis
Tipo de estudio:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
Brief Bioinform
Asunto de la revista:
BIOLOGIA
/
INFORMATICA MEDICA
Año:
2018
Tipo del documento:
Article