在前列腺癌中金雀异黄素上调肿瘤抑制基因MicroRNA-574-3p_千与丸刚志 - 金转停_金雀异黄素Genistein

针对病种：前列腺癌

发表时间：2013年3月

发表国家：美国

登载刊物：公共科学图书馆一

研究单位：美国旧金山退伍军人事务医学中心和加利福尼亚大学泌尿外科等

研究人员：千与丸刚志，柳屋庄一郎，福原一郎，等

主要结论：在此研究中，我们侧重于受金雀异黄素调节的肿瘤抑癌因子miRNA并探究了他们在前列腺癌(PCa) 中的作用和靶向通路。我们的研究结果表明，金雀异黄素上调了靶向几种细胞信号通路的肿瘤抑癌因子miR-574-3p的表达。这些研究结果加深了对金雀异黄素调节PCa中 miRNA 的了解.

Plos One, 2013, 8(3):4422-4427.

Genistein Up-Regulates Tumor Suppressor MicroRNA-574-3p in Prostate Cancer

Takeshi Chiyomaru, Soichiro Yamamura, Shinichiro Fukuhara, 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 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.

美国《公共科学图书馆一》，2013年3月

在前列腺癌中金雀异黄素上调肿瘤抑制基因MicroRNA-574-3p

千与丸刚志，柳屋庄一郎，福原一郎，等

美国旧金山退伍军人事务医学中心和加利福尼亚大学泌尿外科等

金雀异黄素已被证明可以通过改变几种小分子 RNA (miRNAs) 的表达，在体外和体内抑制癌症。在此研究中，我们侧重于受金雀异黄素调节的肿瘤抑癌因子miRNA并探究了他们在前列腺癌(PCa) 中的作用和靶向通路。我们采用 miRNA 基因微阵列分析和实时 RT-PCR技术观察到与空白对照相比，在PCa 细胞中miR-574-3p 被金雀异黄素大幅上调。与正常前列腺细胞 (RWPE-1) 和癌旁正常组织相比，miR-574-3p 的表达在 PCa 细胞和临床 PCa 组织中明显更低。miR-574-3p的低表达水平与肿瘤的晚期和 PCa 标本中较高的格里森评分呈正相关。在体内和体外miR-574-3p在PCa 细胞中的重新表达明显抑制了细胞增殖、迁移和侵袭。miR-574-3p的修复通过减少 Bcl-xL 和激活半胱氨酸蛋白酶-9 和半胱氨酸蛋白酶-3诱导了细胞凋亡。使用 GeneCodis 软件分析，确认了受 miR-574-3p影响的几种途径，如 “癌症途径“、“JAK-STAT 信号传导通路“和 ”Wnt 信号通路“。荧光素酶记录方法检测表明，miR-574-3p 直接绑定到几个靶向基因的 3' UTR（例如 RAC1，EGFR 和 EP300），是“癌症途径“的组成部分。定量实时 PCR 和免疫印迹分析表明，在PCa 细胞中，三种靶向基因的mRNA 和蛋白表达水平被miR-574-3p明显下调。损失函数研究表明三个靶向基因明显影响了PCa 细胞增殖、迁移和侵袭。我们的研究结果表明，金雀异黄素上调了靶向几种细胞信号通路的肿瘤抑癌因子miR-574-3p的表达。这些研究结果加深了对金雀异黄素调节PCa中 miRNA 的了解。