MicroRNA-320 suppresses the stem cell-like characteristics of prostate cancer cells by downregulating the Wnt/beta-catenin signaling pathway.
Carcinogenesis
; 34(3): 530-8, 2013 Mar.
Article
em En
| MEDLINE
| ID: mdl-23188675
ABSTRACT
Prostate cancer (PCa) is a leading cause of mortality and morbidity in men worldwide, and emerging evidence suggests that the CD44(high) prostate tumor-initiating cells (TICs) are associated with its poor prognosis. Although microRNAs are frequently dysregulated in human cancers, the influence of microRNAs on PCa malignancy and whether targeting TIC-associated microRNAs inhibit PCa progression remain unclear. In this study, we found that miR-320 is significantly downregulated in PCa. Overexpression of miR-320 in PCa cells decreases PCa tumorigenesis in vitro and in vivo. Global gene expression profiling of miR-320-overexpressing PCa cells reveals that downstream target genes of Wnt/ß-catenin pathway and cancer stem cell markers are significantly decreased. MicroRNA-320 inhibits ß-catenin expression by targeting the 3'-untranslated region of ß-catenin mRNA. The reduction of miR-320 associated with increased ß-catenin was also found in CD44(high) subpopulation of prostate cancer cells and clinical PCa specimens. Interestingly, knockdown of miR-320 significantly increases the cancer stem-like properties, such as tumorsphere formation, chemoresistance and tumorigenic abilities, although enriching the population of stem-like TICs among PCa cells. Furthermore, increased miR-320 expression in prostate stem-like TICs significantly suppresses stem cell-like properties of PCa cells. These results support that miR-320 is a key negative regulator in prostate TICs, and suggest developing miR-320 as a novel therapeutic agent may offer benefits for PCa treatment.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Células-Tronco Neoplásicas
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Regulação para Baixo
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MicroRNAs
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Via de Sinalização Wnt
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article