Up-regulation of E-cadherin by small activating RNA inhibits cell invasion and migration in 5637 human bladder cancer cells
Up-regulation of E-cadherin by small activating RNA inhibits cell invasion and migration in 5637 human bladder cancer cells
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小激活RNA上调E-钙粘蛋白抑制5637人膀胱癌细胞的细胞侵袭和迁移
DOI：
10.1016/j.bbrc.2008.08.059
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发表时间：
2008-10-31
影响因子：
3.1
通讯作者：
Xie, Liping
中科院分区：
文献类型：
--
作者：
Mao, Qiqi;Li, Yubing;Xie, Liping
最近的研究报道，化学合成的与靶基因启动子互补的小双链RNA可以特异性地诱导多种癌细胞系中的基因表达。这种dsRNA，称为小激活RNA（saRNA），参与最近描述的称为RNA激活（RNAa）的现象。最近的研究表明，saRNA可以通过上调人膀胱癌细胞中的p21（WAF 1/CIP 1）（p21）来抑制细胞增殖和活力。在本研究中，我们证明了由saRNA诱导的E-cadherin表达导致5637人膀胱癌细胞在体外的迁移和侵袭的抑制。在转染靶向E-钙粘蛋白启动子的21个核苷酸的dsRNA（dsE-cad）后，在转录和蛋白质水平证实了E-钙粘蛋白表达的升高。此外，这种抑制作用与β-连环蛋白从细胞核到质膜的重新定位和β-连环蛋白介导的反式激活的降低有关。这些数据表明，通过saRNA激活E-钙粘蛋白可能对膀胱癌和其他类型的癌症具有治疗益处。(C)2008年爱思唯尔公司All rights reserved.
Recent studies have reported that chemically synthesized small duplex RNAs complementary to promoters of target genes can specifically induce gene expression in several cancer cell lines. Such dsRNA, referred to as small activating RNA (saRNA), are involved in the recently described phenomenon called RNA activation (RNAa). Recent findings show that saRNA can inhibit cell proliferation and viability via up-regulation of p21(WAF1/CIP1) (p21) in human bladder cancer cells. In the present study, we demonstrate that induction of E-cadherin expression by saRNA leads to suppression of migration and invasion of 5637 human bladder cancer cells in vitro. The elevated E-cadherin expression was confirmed at transcriptional and protein levels after transfection of a 21-nucleotide dsRNA targeting the E-cadherin promoter (dsE-cad). Furthermore, this inhibitory effect was associated with relocalization of beta-catenin from the nucleus to the plasma membrane and decreased beta-catenin-mediated transactivation. These data suggest that activation of E-cadherin by saRNA may have a therapeutic benefit for bladder and other types of cancer. (C) 2008 Elsevier Inc. All rights reserved.