Genistein downregulates onco-miR-1260b and inhibits Wnt-signalling in renal cancer cells.
Br J Cancer
; 108(10): 2070-8, 2013 May 28.
Article
em En
| MEDLINE
| ID: mdl-23591200
ABSTRACT
BACKGROUND:
Wnt-signalling has an important role in renal cancer and it is modulated by genistein in other cancers. Recently, microRNAs (miRNAs) have emerged as new regulators of gene expression. Thus, we focused on miRNAs to examine the regulatory mechanism of genistein on the Wnt-signalling pathway in renal cell carcinoma (RCC).METHODS:
Initially, we investigated the effect of genistein on Wnt-signalling (TOPflash reporter assay (TCF reporter assays)) in renal cancer cells, and using microarray identified candidate miRNAs whose expression was decreased by genistein. We performed functional analyses and investigated the relationship between miRNA expression and renal cancer patient outcomes. We also did 3'UTR luciferase assays to look at direct miRNA regulation of Wnt-signalling-related genes.RESULTS:
Genistein promoted apoptosis while inhibiting RCC cell proliferation and invasion. Genistein also decreased TCF reporter activity in RCC cells. We found that miR-1260b was highly expressed and significantly downregulated by genistein in RCC cells. The expression of miR-1260b was significantly higher in renal cancer tissues compared with normal, and significantly related to overall shorter survival. In addition, miR-1260b promoted renal cancer cell proliferation and invasion in RCC cells. The 3'UTR luciferase activity of target genes (sFRP1, Dkk2, Smad4) was significantly decreased and their protein expression significantly upregulated in miR-1260b inhibitor-transfected renal cancer cells.CONCLUSION:
Our data suggest that genistein inhibited Wnt-signalling by regulating miR-1260b expression in renal cancer cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma de Células Renais
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Genisteína
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MicroRNAs
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Via de Sinalização Wnt
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Neoplasias Renais
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Br J Cancer
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos