Genistein inhibits prostate cancer cell growth by targeting miR-34a and oncogenic HOTAIR.
Genistein inhibits prostate cancer cell growth by targeting miR-34a and oncogenic HOTAIR.
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DOI：
10.1371/journal.pone.0070372
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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;Yoshino H;Kinoshita T;Majid S;Saini S;Chang I;Tanaka Y;Enokida H;Seki N;Nakagawa M;Dahiya R
染料木素是一种大豆异黄酮，在体内和体外都具有抗肿瘤活性。研究表明染料木素通过调节多种细胞信号通路和microrna （miRNAs）抑制多种类型的癌症，包括前列腺癌（PCa）。最近的研究表明，长链非编码rna （lncRNAs）也参与了许多细胞过程。目前还没有关于gensitein、mirna和lncrna之间关系的报道。在本研究中，我们重点研究了染料木素调控的mirna、lncRNA在PCa中的功能作用。微阵列（SurePrint G3 Human GE 8×60K）用于染料木素处理和对照PCa细胞（PC3和DU145）的表达谱分析。用PCa细胞系、PC3和DU145进行功能实验（细胞增殖、迁移、侵袭、凋亡和细胞周期实验）。体外和体内（裸鼠）模型均用于生长测定。荧光素酶报告基因检测用于miR-34a与HOTAIR的结合。LncRNA分析显示，HOTAIR受染料母素的高度调控，其在去势抵抗PCa细胞系中的表达高于正常前列腺细胞。HOTAIR的siRNA敲低可抑制PCa细胞的增殖、迁移和侵袭，诱导细胞凋亡和细胞周期阻滞。miR-34a也被染料木黄酮上调，可能在PC3和DU145 PCa细胞中直接靶向HOTAIR。我们的研究结果表明染料木素通过下调致癌HOTAIR来抑制PCa细胞的生长，而HOTAIR也是肿瘤抑制因子miR-34a的靶点。这些发现增强了对染料木素在PCa中调控lncRNA HOTAIR和miR-34a的理解。
Genistein is a soy isoflavone that has antitumor activity both in vitro and in vivo. It has been shown that genistein inhibits many type of cancers including prostate cancer (PCa) by regulating several cell signaling pathways and microRNAs (miRNAs). Recent studies suggest that the long non-coding RNAs (lncRNAs) are also involved in many cellular processes. At present there are no reports about the relationship between gensitein, miRNAs and lncRNAs. In this study, we focused on miRNAs, lncRNA that are regulated by genistein and investigated their functional role in PCa. Microarray (SurePrint G3 Human GE 8×60K) was used for expression profiling of genistein treated and control PCa cells (PC3 and DU145). Functional assay (cell proliferation, migration, invasion, apoptosis and cell cycle assays) were performed with the PCa cell lines, PC3 and DU145. Both in vitro and in vivo (nude mouse) models were used for growth assays. Luciferase reporter assays were used for binding of miR-34a to HOTAIR. LncRNA profiling showed that HOTAIR was highly regulated by genistein and its expression was higher in castration-resistant PCa cell lines than in normal prostate cells. Knockdown (siRNA) of HOTAIR decreased PCa cell proliferation, migration and invasion and induced apoptosis and cell cycle arrest. miR-34a was also up-regulated by genistein and may directly target HOTAIR in both PC3 and DU145 PCa cells. Our results indicated that genistein inhibited PCa cell growth through down-regulation of oncogenic HOTAIR that is also targeted by tumor suppressor miR-34a. These findings enhance understanding of how genistein regulates lncRNA HOTAIR and miR-34a in PCa.
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影响因子：
8
作者：
Braconi, C.;Kogure, T.;Valeri, N.;Huang, N.;Nuovo, G.;Costinean, S.;Negrini, M.;Miotto, E.;Croce, C. M.;Patel, T.
通讯作者：
Patel, T.
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：
64.8
作者：
通讯作者：
--
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
影响因子：
5.2
作者：
Lai, Yunli;Zhang, Xuerong;Feng, Youji
通讯作者：
Feng, Youji