RBM38 is involved in TGF-ß-induced epithelial-to-mesenchymal transition by stabilising zonula occludens-1 mRNA in breast cancer.
Br J Cancer
; 117(5): 675-684, 2017 Aug 22.
Article
em En
| MEDLINE
| ID: mdl-28683467
ABSTRACT
BACKGROUND:
The transforming growth factor-ß (TGF-ß) pathway plays a vital role in driving cancer cell epithelial-mesenchymal transition (EMT). Zonula occludens-1 (ZO-1), which is downregulated in response to TGF-ß, is able to control endothelial cell-cell tension, cell migration, and barrier formation. However, the molecular mechanism of how TGF-ß regulates ZO-1 expression remains unclear.METHODS:
Breast cancer cells were treated with TGF-ß to induce an EMT progress. Chromatin immunoprecipitation and dual-luciferase reporter assay were performed to investigate direct relationship between Snail and RNA binding motif protein 38 (RBM38). The RNA immunoprecipitation combined with RNA electrophoretic mobility shift assay and dual-luciferase reporter assay were conducted to testify direct relationship between RBM38 and ZO-1. The ZO-1 siRNA was transfected to breast cancer cells that overexpress RBM38 and the control, followed by transwell and Matrigel invasion assays to examine cell migratory and invasive ability.RESULTS:
Transforming growth factor-ß induced a remarkable downregulation of RBM38 in breast cancer that was directly regulated by transcription repressor Snail targeting the E-box elements in promoter region of RBM38 gene. Additionally, RBM38 positively regulated ZO-1 transcript via directly binding to AU/U-rich elements in its mRNA 3'-UTR. Moreover, by magnifying RBM38 expression, cell migration and invasion mediated by knockdown of ZO-1 in breast cancer were reversed.CONCLUSIONS:
All the results clarified a linear regulation relationship among Snail, RBM38, and ZO-1, implicating RBM38 as a pivotal mediator in TGF-ß-induced EMT in breast cancer.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA Mensageiro
/
Proteínas de Ligação a RNA
/
Transição Epitelial-Mesenquimal
/
Proteína da Zônula de Oclusão-1
Limite:
Female
/
Humans
Idioma:
En
Revista:
Br J Cancer
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
China