A combinatorially regulated RNA splicing signature predicts breast cancer EMT states and patient survival.
RNA
; 26(9): 1257-1267, 2020 09.
Article
em En
| MEDLINE
| ID: mdl-32467311
ABSTRACT
During breast cancer metastasis, the developmental process epithelial-mesenchymal transition (EMT) is abnormally activated. Transcriptional regulatory networks controlling EMT are well-studied; however, alternative RNA splicing also plays a critical regulatory role during this process. A comprehensive understanding of alternative splicing (AS) and the RNA binding proteins (RBPs) that regulate it during EMT and their impact on breast cancer remains largely unknown. In this study, we annotated AS in the breast cancer TCGA data set and identified an AS signature that is capable of distinguishing epithelial and mesenchymal states of the tumors. This AS signature contains 25 AS events, among which nine showed increased exon inclusion and 16 showed exon skipping during EMT. This AS signature accurately assigns the EMT status of cells in the CCLE data set and robustly predicts patient survival. We further developed an effective computational method using bipartite networks to identify RBP-AS networks during EMT. This network analysis revealed the complexity of RBP regulation and nominated previously unknown RBPs that regulate EMT-associated AS events. This study highlights the importance of global AS regulation during EMT in cancer progression and paves the way for further investigation into RNA regulation in EMT and metastasis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
RNA
/
Processamento Alternativo
/
Transição Epitelial-Mesenquimal
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
RNA
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos