Identification of NDRG1-regulated genes associated with invasive potential in cervical and ovarian cancer cells
Identification of NDRG1-regulated genes associated with invasive potential in cervical and ovarian cancer cells
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鉴定与宫颈癌和卵巢癌细胞侵袭潜力相关的 NDRG1 调控基因
DOI：
10.1016/j.bbrc.2011.03.140
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发表时间：
2011-04-29
影响因子：
3.1
通讯作者：
Zhao, Zheng
中科院分区：
文献类型：
--
作者：
Zhao, Gang;Chen, Jiawei;Zhao, Zheng
N-myc下游调节基因1（NDRG 1）是调节肿瘤侵袭的重要基因。本研究利用shRNA技术抑制宫颈癌细胞系CaSki和卵巢癌细胞系HO-8910 PM中NDRG 1的表达。体外实验表明，NDRG 1敲低增强了肿瘤细胞的粘附、迁移和侵袭活性，而不影响细胞增殖。cDNA微阵列分析显示，NDRG 1敲低后，两种细胞系中有96个失调控基因发生了2倍以上的变化。10个常见的上调基因（LPXN、DDR2、COL 6A 1、IL 6、IL 8、FYN、PTP 4A 3、PAPPA、ETV 5和CYGB）和一个常见的下调基因（CLCA 2）被认为增强肿瘤细胞侵袭活性。BisoGenet网络分析表明NDRG 1以间接方式调控这些入侵效应基因/蛋白。此外，NDRG 1敲低还降低了促侵袭基因如MMP 7、TMPRSS 4和CTSK的表达。这些结果表明NDRG 1对侵袭和转移的调节是一个高度复杂的过程。(C)2011 Elsevier Inc. All rights reserved.
N-myc downstream regulated gene 1 (NDRG1) is an important gene regulating tumor invasion. In this study, shRNA technology was used to suppress NDRG1 expression in CaSki (a cervical cancer cell line) and HO-8910PM (an ovarian cancer cell line). In vitro assays showed that NDRG1 knockdown enhanced tumor cell adhesion, migration and invasion activities without affecting cell proliferation. cDNA microarray analysis revealed 96 deregulated genes with more than 2-fold changes in both cell lines after NDRG1 knockdown. Ten common upregulated genes (LPXN, DDR2, COL6A1,IL6,IL8, FYN, PTP4A3, PAPPA, ETV5 and CYGB) and one common downregulated gene (CLCA2) were considered to enhance tumor cell invasive activity. BisoGenet network analysis indicated that NDRG1 regulated these invasion effector genes/proteins in an indirect manner. Moreover, NDRG1 knockdown also reduced pro-invasion genes expression such as MMP7, TMPRSS4 and CTSK. These results suggest that regulation of invasion and metastasis by NDRG1 is a highly complicated process. (C) 2011 Elsevier Inc. All rights reserved.