Genistein up-regulates tumor suppressor microRNA-574-3p in prostate cancer.
Genistein up-regulates tumor suppressor microRNA-574-3p in prostate cancer.
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DOI：
10.1371/journal.pone.0058929
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发表时间：
2013
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;Fukuhara S;Hidaka H;Majid S;Saini S;Arora S;Deng G;Shahryari V;Chang I;Tanaka Y;Tabatabai ZL;Enokida H;Seki N;Nakagawa M;Dahiya R
染料木黄酮已被证明通过改变几种microRNA（miRNA）的表达在体外和体内抑制癌症。在本研究中，我们专注于由染料木素调控的肿瘤抑制miRNA，并研究它们在前列腺癌（PCa）中的功能和靶向通路。利用miRNA微阵列分析和实时RT-PCR，我们观察到miR-574- 3 p在用染料木素处理的PCa细胞中与载体对照相比显著上调。与正常前列腺细胞（RWPE-1）和癌旁正常组织相比，PCa细胞系和临床PCa组织中miR-574- 3 p的表达显著降低。miR-574- 3 p的低表达水平与PCa中晚期肿瘤分期和较高的Gleason评分相关。在PCa细胞中重新表达miR-574- 3 p在体外和体内均显著抑制细胞增殖、迁移和侵袭。miR-574- 3 p恢复通过减少Bcl-xL和激活caspase-9和caspase-3诱导细胞凋亡。使用GeneCodis软件分析，确定了受miR-574- 3 p影响的几种途径，如“癌症中的途径”、“Jak-STAT信号通路”和“Wnt信号通路”。荧光素酶报告基因分析表明，miR-574- 3 p直接结合到几个靶基因（如RAC 1、EGFR和EP 300）的3′ UTR上，这些靶基因是“癌症通路”的组成部分。实时荧光定量PCR和Western分析显示，miR-574- 3 p可显著下调PCa细胞中3个靶基因的mRNA和蛋白表达水平。功能丧失研究表明，这三个靶基因显着影响PCa细胞系的细胞增殖、迁移和侵袭。我们的研究结果表明，染料木黄酮上调肿瘤抑制因子miR-574- 3 p的表达，靶向几个细胞信号通路。这些发现增强了对染料木黄酮如何调控PCa中miRNA的理解。
Genistein has been shown to inhibit cancers both in vitro and in vivo, by altering the expression of several microRNAs (miRNAs). In this study, we focused on tumor suppressor miRNAs regulated by genistein and investigated their function in prostate cancer (PCa) and target pathways. Using miRNA microarray analysis and real-time RT-PCR we observed that miR-574-3p was significantly up-regulated in PCa cells treated with genistein compared with vehicle control. The expression of miR-574-3p was significantly lower in PCa cell lines and clinical PCa tissues compared with normal prostate cells (RWPE-1) and adjacent normal tissues. Low expression level of miR-574-3p was correlated with advanced tumor stage and higher Gleason score in PCa specimens. Re-expression of miR-574-3p in PCa cells significantly inhibited cell proliferation, migration and invasion in vitro and in vivo. miR-574-3p restoration induced apoptosis through reducing Bcl-xL and activating caspase-9 and caspase-3. Using GeneCodis software analysis, several pathways affected by miR-574-3p were identified, such as ‘Pathways in cancer’, ‘Jak-STAT signaling pathway’, and ‘Wnt signaling pathway’. Luciferase reporter assays demonstrated that miR-574-3p directly binds to the 3′ UTR of several target genes (such as RAC1, EGFR and EP300) that are components of ‘Pathways in cancer’. Quantitative real-time PCR and Western analysis showed that the mRNA and protein expression levels of the three target genes in PCa cells were markedly down-regulated with miR-574-3p. Loss-of-function studies demonstrated that the three target genes significantly affect cell proliferation, migration and invasion in PCa cell lines. Our results show that genistein up-regulates tumor suppressor miR-574-3p expression targeting several cell signaling pathways. These findings enhance understanding of how genistein regulates with miRNA in PCa.
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染料木黄酮通过抑制致癌性microRNA-151抑制前列腺癌的生长。
影响因子：
3.7
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
通讯作者：
Dahiya R
影响因子：
4.1
作者：
Cho, William C. S.;Chow, Andrew S. C.;Au, Joseph S. K.
通讯作者：
Au, Joseph S. K.
DOI：
10.1016/j.jnutbio.2012.03.002
发表时间：
2012-07
期刊：
The Journal of nutritional biochemistry
影响因子：
--
作者：
Kim YS;Farrar W;Colburn NH;Milner JA
通讯作者：
Milner JA
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
5.6
作者：
Guo, Yanping;Wang, Shihua;Clinton, Steven K.
通讯作者：
Clinton, Steven K.