miR-214 and hypoxia down-regulate Necl-2/CADM1 and enhance ErbB2/ErbB3 signaling.
Genes Cells
; 18(3): 195-202, 2013 Mar.
Article
en En
| MEDLINE
| ID: mdl-23301758
ABSTRACT
Necl-2/CADM1 is down-regulated by the promoter hypermethylation and/or the loss of heterozygosity at chromosome 11q23.2 in many types of cancers and serves as a tumor suppressor by interacting in cis with ErbB3 and suppressing the ligand-induced ErbB2/ErbB3 signaling for cell movement and death. However, the incidence of these epigenetic and genetic abnormalities of Necl-2 is 30-60% in these cancers. We investigated here other mechanisms that down-regulate Necl-2. miR-214, that is frequently up-regulated in a variety of cancers, targeted the 3'UTR of the Necl-2 mRNA directly, suppressed the translation of Necl-2 and enhanced the ligand-induced ErbB2/ErbB3 signaling in human colon cancer Caco-2 cells. Hypoxia reduced the Necl-2 protein level in a manner independent of miR-214 or hypoxia-inducible factor-1α in Caco-2 cells. These results indicate that miR-214 and hypoxia are novel regulators that down-regulate Necl-2 and enhance ErbB2/ErbB3 signaling.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Inmunoglobulinas
/
Moléculas de Adhesión Celular
/
Regulación hacia Abajo
/
Receptor ErbB-2
/
Receptor ErbB-3
/
MicroARNs
Límite:
Humans
Idioma:
En
Revista:
Genes Cells
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2013
Tipo del documento:
Article
País de afiliación:
Japón