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- Title
Genistein suppresses prostate cancer growth through inhibition of oncogenic microRNA-151.
- Authors
Chiyomaru, Takeshi; Yamamura, Soichiro; Zaman, Mohd Saif; Majid, Shahana; Deng, Guoren; Shahryari, Varahram; Saini, Sharanjot; Hirata, Hiroshi; Ueno, Koji; Chang, Inik; Tanaka, Yuichiro; Tabatabai, Z Laura; Enokida, Hideki; Nakagawa, Masayuki; Dahiya, Rajvir
- Abstract
Genistein has been shown to suppress the growth of several cancers through modulation of various pathways. However, the effects of genistein on the regulation of oncogenic microRNA-151 (miR-151) have not been reported. In this study, we investigated whether genistein could alter the expression of oncogenic miR-151 and its target genes that are involved in the progression and metastasis of prostate cancer (PCa). Real-time RT-PCR showed that the expression of miR-151 was higher in PC3 and DU145 cells compared with RWPE-1 cells. Treatment of PC3 and DU145 cells with 25 µM genistein down-regulated the expression of miR-151 compared with vehicle control. Inhibition of miR-151 in PCa cells by genistein significantly inhibited cell migration and invasion. In-silico analysis showed that several genes (CASZ1, IL1RAPL1, SOX17, N4BP1 and ARHGDIA) suggested to have tumor suppressive functions were target genes of miR-151. Luciferase reporter assays indicated that miR-151 directly binds to specific sites on the 3'UTR of target genes. Quantitative real-time PCR analysis showed that the mRNA expression levels of the five target genes in PC3 and DU145 were markedly changed with miR-151 mimics and inhibitor. Kaplan-Meier curves and log-rank tests revealed that high expression levels of miR-151 had an adverse effect on survival rate. This study suggests that genistein mediated suppression of oncogenic miRNAs can be an important dietary therapeutic strategy for the treatment of PCa.
- Publication
PloS one, 2012, Vol 7, Issue 8, pe43812
- ISSN
1932-6203
- Publication type
Journal Article
- DOI
10.1371/journal.pone.0043812