Genistein suppresses prostate cancer growth through inhibition of oncogenic microRNA-151.
Genistein suppresses prostate cancer growth through inhibition of oncogenic microRNA-151.
复制标题
染料木黄酮通过抑制致癌性microRNA-151抑制前列腺癌的生长。
DOI：
10.1371/journal.pone.0043812
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Dahiya R
中科院分区：
文献类型：
--
作者：
Chiyomaru T;Yamamura S;Zaman MS;Majid S;Deng G;Shahryari V;Saini S;Hirata H;Ueno K;Chang I;Tanaka Y;Tabatabai ZL;Enokida H;Nakagawa M;Dahiya R
金雀异黄素已被证明可以通过调节各种途径来抑制多种癌症的生长。然而，金雀异黄素对致癌 microRNA-151 (miR-151) 的调节作用尚未见报道。在这项研究中，我们研究了金雀花素是否可以改变致癌 miR-151 及其靶基因的表达，这些基因参与前列腺癌 (PCa) 的进展和转移。实时RT-PCR显示，与RWPE-1细胞相比，PC3和DU145细胞中miR-151的表达更高。与载体对照相比，用 25 µM 金雀异黄素处理 PC3 和 DU145 细胞可下调 miR-151 的表达。金雀异黄素抑制 PCa 细胞中的 miR-151 显着抑制细胞迁移和侵袭。计算机分析显示，几个具有肿瘤抑制功能的基因（CASZ1、IL1RAPL1、SOX17、N4BP1 和 AHGDIA）是 miR-151 的靶基因。荧光素酶报告基因检测表明 miR-151 直接结合靶基因 3'UTR 上的特定位点。实时定量PCR分析表明，miR-151模拟物和抑制剂使PC3和DU145中5个靶基因的mRNA表达水平发生显着变化。 Kaplan-Meier 曲线和时序检验表明，miR-151 的高表达水平对生存率有不利影响。这项研究表明金雀异黄素介导的致癌 miRNA 抑制可能是治疗 PCa 的重要饮食治疗策略。
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.
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影响因子：
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