MicroRNA 375 mediates the signaling pathway of corticotropin-releasing factor (CRF) regulating pro-opiomelanocortin (POMC) expression by targeting mitogen-activated protein kinase 8.
J Biol Chem
; 288(15): 10361-73, 2013 Apr 12.
Article
em En
| MEDLINE
| ID: mdl-23430746
ABSTRACT
Pro-opiomelanocortin (POMC) is a common precursor of melanocortin-related peptides in the pituitary and primarily regulated by corticotropin- releasing factor (CRF). Our results show that miR-375 is highly expressed in the mouse pituitary gland and located specifically in the intermediate lobe of pituitary. The functional studies show that the forced inhibition of endogenous miR-375 in AtT-20 mouse pituitary tumor cells and in the intermediate lobe of the pituitary gland significantly increases POMC expression, whereas miR-375 overexpression down-regulates POMC expression and ACTH secretion stimulated by CRF. This function of miR-375 is accomplished by its binding to the 3'-UTR of mitogen-activated protein kinase kinase kinase-8. Our results here have demonstrated that miR-375 acts as a negative regulating molecule mediating the signaling pathway of CRF and affecting POMC expression by targeting mitogen-activated protein kinase kinase kinase-8, which subsequently down-regulates ERK1/2 phosphorylation and nerve growth factor-induced clone B (NGFI-B) transcription activity. Taken together, our results show that miR-375 is a novel negative regulator of POMC expression and related hormone secretion.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Hipófise
/
Pró-Opiomelanocortina
/
Hormônio Liberador da Corticotropina
/
Regulação da Expressão Gênica
/
Sistema de Sinalização das MAP Quinases
/
MicroRNAs
/
Proteína Quinase 8 Ativada por Mitógeno
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article