miR-338-3p suppresses gastric cancer progression through a PTEN-AKT axis by targeting P-REX2a.
Mol Cancer Res
; 12(3): 313-21, 2014 Mar.
Article
em En
| MEDLINE
| ID: mdl-24375644
ABSTRACT
UNLABELLED Results from recent studies suggest that aberrant microRNA expression is common in numerous cancers. Although miR-338-3p has been implicated in hepatocellular carcinoma, its role in gastric cancer is unknown. To this end, we report that miR-338-3p is downregulated in both gastric cancer tissue and cell lines. Forced expression of miR-338-3p inhibited cell proliferation and clonogenicity and induced a G1-S arrest as well as apoptosis in gastric cancer cells. Furthermore, P-Rex2a (PREX2) was identified as a direct target of miR-338-3p, and silencing P-Rex2a resulted in the same biologic effects of miR-338-3p expression in gastric cancer cells. Furthermore, both enforced expression of miR-338-3p or silencing of P-Rex2a resulted in activation of PTEN, leading to a decline in AKT phosphorylation. Also, miR-338-3p markedly inhibited the in vivo tumorigenicity in a nude mouse xenograft model system. These results demonstrate that miR-338-3p affects gastric cancer progression through PTEN-AKT signaling by targeting P-Rex2a in gastric cancer cells, which posits miR-338-3p as a novel strategy for gastric cancer treatment. IMPLICATIONS miR-338-3p acts as a novel tumor suppressor that blocks the growth of gastric cancer cells through PTEN-PI3K signaling by targeting P-Rex2a.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
/
Proteínas Tirosina Quinases
/
Fatores de Troca do Nucleotídeo Guanina
/
MicroRNAs
/
PTEN Fosfo-Hidrolase
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Mol Cancer Res
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
China