Suppression of RND3 activity by AES downregulation promotes cancer cell proliferation and invasion
Suppression of RND3 activity by AES downregulation promotes cancer cell proliferation and invasion
复制标题
通过 AES 下调抑制 RND3 活性可促进癌细胞增殖和侵袭。
DOI：
10.3892/ijmm.2013.1321
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发表时间：
2013-05-01
影响因子：
5.4
通讯作者：
Bi, Feng
中科院分区：
文献类型：
--
作者：
Xia, Hongwei;Li, Mingxing;Bi, Feng
分裂的氨基末端增强子(AES)是Groucho/TLE家族的成员。虽然它没有DNA结合位点，但它可以通过与转录因子相互作用来调节转录活性。新的证据表明，AES可能在肿瘤转移中发挥重要作用，但其分子机制尚不清楚。在这项研究中，我们发现通过RNA干扰(RNAi)抑制AES在两种癌细胞株MDA-MB-231和HepG2的mRNA和蛋白质水平上下调RND3的表达。此外，荧光素酶分析表明，过表达的AES显著增强了RND3启动子的活性。此外，RNAi抑制MDA-MB-231和HepG2细胞中的AES显著促进细胞增殖、细胞周期进展和侵袭，这与RNAi介导的RND3基因敲除在这些细胞中的作用一致。首次提供的数据表明，AES改变癌细胞的恶性行为与RND3调控有关，这些发现也为AES调节肿瘤恶性的机制提供了新的见解。
Amino-terminal enhancer of split (AES) is a member of the Groucho/TLE family. Although it has no DNA-binding site, AES can regulate transcriptional activity by interacting with transcriptional factors. Emerging evidence indicates that AES may play an important role in tumor metastasis, but the molecular mechanism is still poorly understood. In this study, we found that knockdown of AES by RNA interference (RNAi) downregulated RND3 expression at the mRNA and protein levels in MDA-MB-231 and HepG2, two cancer cell lines. Furthermore, luciferase assays showed that overexpression of AES significantly enhanced RND3 promoter activity. Moreover, inhibition of AES both in MDA-MB-231 and HepG2 cells by RNAi significantly promoted cell proliferation, cell cycle progression and invasion, consistent with the effects of RNAi-mediated RND3 knockdown in these cells. For the first time, data are presented showing that alteration of the malignant behavior of cancer cells by AES is related to RND3 regulation, and these findings also provide new insights into the mechanism of AES action in regulating tumor malignancy.