LEF1 Targeting EMT in Prostate Cancer Invasion Is Regulated by miR-34a.
Mol Cancer Res
; 13(4): 681-8, 2015 Apr.
Article
em En
| MEDLINE
| ID: mdl-25587085
ABSTRACT
UNLABELLED The microRNA-34a (miR-34a), a tumor-suppressive microRNA (miRNA), is implicated in epithelial-mesenchymal transition (EMT) and cancer stem cells. Lymphoid enhancer-binding factor-1 (LEF1) is a key transcription factor in the Wnt signaling pathway, and has been suggested to be involved in regulation of cell proliferation and invasion. Here, the molecular mechanism of miR-34a and LEF1 in cooperatively regulating prostate cancer cell invasion is described. Molecular profiling analysis of miRNA levels in prostate cancer cells revealed a negative correlation between miR-34a and LEF1 expression, and the downregulation of LEF1 by miR-34a was confirmed by luciferase assays. Furthermore, miR-34a specifically repressed LEF1 expression through direct binding to its 3'-untranslated regions (3'-UTR). miR-34a modulated the levels of LEF1 to regulate EMT in prostate cancer cells. Functionally, miR-34a negatively correlated with the migration and invasion of prostate cancer cells through LEF1. An analysis of miR-34a expression levels in matched human tumor and benign tissues demonstrated consistent and statistically significant downregulation of miR-34a in primary prostate cancer specimens. These data strongly suggest that miR-34a/LEF1 regulation of EMT plays an important role in prostate cancer migration and invasion. IMPLICATIONS The miR-34a-LEF1 axis represents a potential molecular target for novel therapeutic strategies in prostate cancer.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
MicroRNAs
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Fator 1 de Ligação ao Facilitador Linfoide
/
Transição Epitelial-Mesenquimal
Limite:
Humans
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Male
Idioma:
En
Revista:
Mol Cancer Res
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
China