title: Genistein suppresses prostate cancer growth through inhibition of oncogenic microRNA-151.
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.
authors.affiliation: Department of Urology, San Francisco Veterans Affairs Medical Center and University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Chiyomaru
authors.forename: Soichiro
authors.initials: S
authors.lastname: Yamamura
authors.forename: Mohd Saif
authors.initials: MS
authors.lastname: Zaman
authors.forename: Shahana
authors.initials: S
authors.lastname: Majid
authors.forename: Guoren
authors.initials: G
authors.lastname: Deng
authors.forename: Varahram
authors.initials: V
authors.lastname: Shahryari
authors.forename: Sharanjot
authors.initials: S
authors.lastname: Saini
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hirata
authors.forename: Koji
authors.initials: K
authors.lastname: Ueno
authors.forename: Inik
authors.initials: I
authors.lastname: Chang
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Z Laura
authors.initials: ZL
authors.lastname: Tabatabai
authors.forename: Hideki
authors.initials: H
authors.lastname: Enokida
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Rajvir
authors.initials: R
authors.lastname: Dahiya
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D019295:Computational Biology; D018450:Disease Progression; D055785:Gene Knockdown Techniques; D017930:Genes, Reporter / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009857:Oncogenes / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; C548886:MIRN151a microRNA, human; D035683:MicroRNAs; D019833:Genistein; D008156:Luciferases