Plos One, 2012, 7(8):e43812.

Genistein Suppresses Prostate Cancer Growth through Inhibition of Oncogenic MicroRNA-151

Takeshi Chiyomaru, Mohd Zaman, Shahana Majid, et al

Department of Urology, San Francisco Veterans Affairs Medical Center and University of California San Francisco, San Francisco, California, United States of America; et al

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.

美国《公共科学图书馆一》，2012年8月

金雀异黄素通过抑制致癌基因MicroRNA-151抑制前列腺癌的生长

武志 千与丸，穆赫德 萨曼，沙哈纳  马吉德，等

美国旧金山退伍军人事务医学中心泌尿外科和加利福尼亚大学等

已证明金雀异黄素通过调节的多种途径抑制几种癌症细胞的生长。然而，金雀异黄素对致癌基因微 RNA-151 (miR-151) 调节的影响还没有报道。在本研究中，我们探究了金雀异黄素是否能改变致癌基因miR-151 的表达及与前列腺癌 (PCa)侵袭及转移相关的靶向基因。实时逆转录-聚合酶链反应表明，miR-151的表达在PC3 和 DU145 细胞中比在 RWPE-1 细胞更高。用25 uM金雀异黄素 处理PC3 和 DU145 细胞，与空白对照样相比miR-151的表达有所下调。金雀异黄素抑制PCa 细胞的miR-151进而明显抑制细胞的迁移和侵袭。在生物信息学分析表明几种基因 （CASZ1、 IL1RAPL1、 SOX17、 N4BP1 和 ARHGDIA）应该拥有以miR151 为靶向基因的肿瘤抑制功能。荧光素酶标记测试表明，miR-151 直接绑定到靶向基因 3′UTR上的特定位点。定量实时 PCR 分析表明 在PC3 和 DU145 中的五个靶向基因的 mRNA 表达水平被miR-151 模仿和抑制剂明显改变。卡普兰-迈耶曲线和时序检验测试表明，miR-151的高水平表达对成活率产生不利影响。这项研究表明，金雀异黄素调节致癌 基因miRNAs的抑制可能是一种饮食治疗PCa的重要战略。