MicroRNA-211 expression promotes colorectal cancer cell growth in vitro and in vivo by targeting tumor suppressor CHD5.
MicroRNA-211 expression promotes colorectal cancer cell growth in vitro and in vivo by targeting tumor suppressor CHD5.
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DOI：
10.1371/journal.pone.0029750
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Gu X
中科院分区：
文献类型：
--
作者：
Cai C;Ashktorab H;Pang X;Zhao Y;Sha W;Liu Y;Gu X
染色体结构域解旋酶DNA结合蛋白5（Chromodomain-helicase-DNA-binding protein 5，CHD 5）是一种新发现的肿瘤抑制因子，在多种人类肿瘤中表达下调。我们的前期工作揭示了CHD 5在大肠癌中的低表达与CHD 5启动子CpG岛高甲基化有关。在这项研究中，我们研究了microRNA-211（miR-211）调控的CHD 5表达对结直肠肿瘤发生的影响。通过TargetScan软件分析预测miR-211靶向CHD 5。使用慢病毒转导产生稳定表达外源性miR-211的结直肠癌细胞系（HCT-116 miR-211），并用作体外和体内研究的模型。与载体对照细胞（HCT-116载体）相比，HCT-116 miR-211细胞中miR-211的表达水平上调了16倍。外源性miR-211直接与CHD 5 mRNA的3′-非翻译区（3′-UTR）结合，导致HCT-116 miR-211细胞中CHD 5蛋白水平降低50%。MTT法、集落形成法、流式细胞术、划痕法和异种移植瘤法检测显示，HCT-116 miR-211细胞在体外和体内的细胞增殖、肿瘤生长和细胞迁移水平均显著高于HCT-116载体细胞。此外，我们发现在HCT-116细胞中强制表达miR-211能够改变p53通路相关的调节蛋白，如MDM 2，Bcl-2，Bcl-xL和Bax。我们的研究结果表明，CHD 5是miR-211调控的直接靶点。miR-211的强制表达至少部分通过下调CHD 5肿瘤抑制因子的表达水平来促进肿瘤细胞生长。我们的研究结果提供了一个更好的理解之间的关联miR-211调节CHD 5的表达和CHD 5的功能在结直肠肿瘤的发生。
Chromodomain-helicase-DNA-binding protein 5 (CHD5) is a newly identified tumor suppressor that is frequently downregulated in a variety of human cancers. Our previous work revealed that the low expression of CHD5 in colorectal cancer is correlated with CHD5 promoter CpG island hypermethylation. In this study, we investigated the effect of microRNA-211 (miR-211)-regulated CHD5 expression on colorectal tumorigenesis. miR-211 was predicted to target CHD5 by TargetScan software analysis. A stably expressing exogenous miR-211 colorectal cancer cell line (HCT-116miR-211) was generated using lentiviral transduction and used as a model for in vitro and in vivo studies. The expression level of miR-211 in HCT-116miR-211 cells was upregulated by 16-fold compared to vector control cells (HCT-116vector). Exogenous miR-211 directly binds to the 3′-untranslated region (3′-UTR) of CHD5 mRNA, resulting in a 50% decrease in CHD5 protein level in HCT-116miR-211 cells. The levels of cell proliferation, tumor growth, and cell migration of HCT-116miR-211 cells were significantly higher than HCT-116vector cells under both in vitro and in vivo conditions, as determined using the methods of MTT, colony formation, flow cytometry, scratch assay, and tumor xenografts, respectively. In addition, we found that enforced expression of miR-211 in HCT-116 cells was able to alter p53 pathway-associated regulatory proteins, such as MDM2, Bcl-2, Bcl-xL, and Bax. Our results demonstrate that CHD5 is a direct target of miR-211 regulation. Enforced expression of miR-211 promotes tumor cell growth at least in part by downregulating the expression level of the CHD5 tumor suppressor. Our results provide a better understanding of the association of between miR-211-regulated CHD5 expression and CHD5 function in colorectal tumorigenesis.
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影响因子：
8
作者：
White, PS;Thompson, PM;Brodeur, GM
通讯作者：
Brodeur, GM
DOI：
10.1158/1940-6207.capr-09-0243
发表时间：
2010-06
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Zhao Y;Hao Y;Ji H;Fang Y;Guo Y;Sha W;Zhou Y;Pang X;Southerland WM;Califano JA;Gu X
通讯作者：
Gu X
影响因子：
64.5
作者：
Bagchi, Anindya;Papazoglu, Cristian;Mills, Alea A.
通讯作者：
Mills, Alea A.
影响因子：
3.7
作者：
Aarts, M;Dannenberg, H;de Krijger, RR
通讯作者：
de Krijger, RR
DOI：
10.1158/1940-6207.capr-10-0333
发表时间：
2011-07
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Hao Y;Gu X;Zhao Y;Greene S;Sha W;Smoot DT;Califano J;Wu TC;Pang X
通讯作者：
Pang X