Genistein downregulates onco-miR-1260b and inhibits Wnt-signalling in renal cancer cells.
Genistein downregulates onco-miR-1260b and inhibits Wnt-signalling in renal cancer cells.
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DOI：
10.1038/bjc.2013.173
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发表时间：
2013-05-28
影响因子：
8.8
通讯作者：
Dahiya R
中科院分区：
文献类型：
--
作者：
Hirata H;Ueno K;Nakajima K;Tabatabai ZL;Hinoda Y;Ishii N;Dahiya R
Wnt 信号传导在肾癌中发挥重要作用，并且在其他癌症中受金雀异黄酮调节。最近，microRNA (miRNA) 已成为基因表达的新调节因子。因此，我们重点关注 miRNA，以研究金雀异黄素对肾细胞癌 (RCC) Wnt 信号通路的调节机制。最初，我们研究了金雀异黄素对肾癌细胞中 Wnt 信号传导的影响（TOPflash 报告基因测定（TCF 报告基因测定）），并使用微阵列鉴定了金雀异黄素表达降低的候选 miRNA。我们进行了功能分析并研究了 miRNA 表达与肾癌患者预后之间的关系。我们还进行了 3'UTR 荧光素酶测定，以观察 miRNA 对 Wnt 信号相关基因的直接调节。金雀异黄素促进细胞凋亡，同时抑制肾细胞癌细胞增殖和侵袭。金雀异黄素还降低了 RCC 细胞中的 TCF 报告基因活性。我们发现 miR-1260b 在 RCC 细胞中高表达并被金雀异黄素显着下调。与正常组织相比，miR-1260b在肾癌组织中的表达显着较高，并且与整体较短的生存期显着相关。此外，miR-1260b促进肾癌细胞增殖和RCC细胞侵袭。在转染miR-1260b抑制剂的肾癌细胞中，靶基因（sFRP1、Dkk2、Smad4）的3'UTR荧光素酶活性显着降低，其蛋白表达显着上调。我们的数据表明金雀异黄素通过调节肾癌细胞中的 miR-1260b 表达来抑制 Wnt 信号传导。
Wnt-signalling has an important role in renal cancer and it is modulated by genistein in other cancers. Recently, microRNAs (miRNAs) have emerged as new regulators of gene expression. Thus, we focused on miRNAs to examine the regulatory mechanism of genistein on the Wnt-signalling pathway in renal cell carcinoma (RCC). Initially, we investigated the effect of genistein on Wnt-signalling (TOPflash reporter assay (TCF reporter assays)) in renal cancer cells, and using microarray identified candidate miRNAs whose expression was decreased by genistein. We performed functional analyses and investigated the relationship between miRNA expression and renal cancer patient outcomes. We also did 3′UTR luciferase assays to look at direct miRNA regulation of Wnt-signalling-related genes. Genistein promoted apoptosis while inhibiting RCC cell proliferation and invasion. Genistein also decreased TCF reporter activity in RCC cells. We found that miR-1260b was highly expressed and significantly downregulated by genistein in RCC cells. The expression of miR-1260b was significantly higher in renal cancer tissues compared with normal, and significantly related to overall shorter survival. In addition, miR-1260b promoted renal cancer cell proliferation and invasion in RCC cells. The 3′UTR luciferase activity of target genes (sFRP1, Dkk2, Smad4) was significantly decreased and their protein expression significantly upregulated in miR-1260b inhibitor-transfected renal cancer cells. Our data suggest that genistein inhibited Wnt-signalling by regulating miR-1260b expression in renal cancer cells.
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影响因子：
10.5
作者：
Linehan WM;Bratslavsky G;Pinto PA;Schmidt LS;Neckers L;Bottaro DP;Srinivasan R
通讯作者：
Srinivasan R
影响因子：
5.7
作者：
Cooper SJ;von Roemeling CA;Kang KH;Marlow LA;Grebe SK;Menefee ME;Tun HW;Colon-Otero G;Perez EA;Copland JA
通讯作者：
Copland JA
影响因子：
8
作者：
Ahmad, I.;Morton, J. P.;Singh, L. B.;Radulescu, S. M.;Ridgway, R. A.;Patel, S.;Woodgett, J.;Winton, D. J.;Taketo, M. M.;Wu, X-R;Leung, H. Y.;Sansom, O. J.
通讯作者：
Sansom, O. J.
影响因子：
4.7
作者：
Majid, Shahana;Dar, Altaf A.;Dahiya, Rajvir
通讯作者：
Dahiya, Rajvir
影响因子：
4.8
作者：
Hassan, Mohammad Q.;Maeda, Yukiko;Lian, Jane B.
通讯作者：
Lian, Jane B.