MiR-130a, miR-203 and miR-205 jointly repress key oncogenic pathways and are downregulated in prostate carcinoma.
Oncogene
; 32(3): 277-85, 2013 Jan 17.
Article
em En
| MEDLINE
| ID: mdl-22391564
ABSTRACT
With â¼30 000 deaths annually in the United States, prostate cancer (PCa) is a major oncologic disease. Here we show that the microRNAs miR-130a, miR-203 and miR-205 jointly interfere with the two major oncogenic pathways in prostate carcinoma and are downregulated in cancer tissue. Using transcriptomics we show that the microRNAs repress several gene products known to be overexpressed in this cancer. Argonaute 2 (AGO2) co-immunoprecipitation, reporter assays and western blot analysis demonstrate that the microRNAs directly target several components of the mitogen-activated protein kinase (MAPK) and androgen receptor (AR) signaling pathways, among those several AR coregulators and HRAS (Harvey rat sarcoma viral oncogene homolog), and repress signaling activity. Both pathways are central for the development of the primary tumor and in particular the progression to its incurable castration-resistant form. Reconstitution of the microRNAs in LNCaP PCa cells induce morphological changes, which resemble the effect of androgen deprivation, and jointly impair tumor cell growth by induction of apoptosis and cell cycle arrest. We therefore propose that these microRNAs jointly act as tumor suppressors in prostate carcinoma and might interfere with progression to castration resistance.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oncogenes
/
Neoplasias da Próstata
/
Transdução de Sinais
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Regulação para Baixo
/
MicroRNAs
Limite:
Humans
/
Male
Idioma:
En
Revista:
Oncogene
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Alemanha