EZH2 depletion blocks the proliferation of colon cancer cells.
EZH2 depletion blocks the proliferation of colon cancer cells.
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DOI：
10.1371/journal.pone.0021651
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Hoppe-Seyler F
中科院分区：
文献类型：
--
作者：
Fussbroich B;Wagener N;Macher-Goeppinger S;Benner A;Fälth M;Sültmann H;Holzer A;Hoppe-Seyler K;Hoppe-Seyler F
据报道，Zeste 2（EZH 2）蛋白的增强子刺激某些癌症中的细胞生长，因此被认为是治疗干预的有趣的新靶点。在这里，我们研究了EZH 2对结肠癌细胞生长控制的可能作用。RNA干扰（RNAi）介导的细胞内EZH 2耗竭导致结肠癌细胞在G1/S转换的细胞周期停滞。这与瞬时转染合成的EZH 2靶向siRNA后细胞数量的减少以及载体携带的siRNA稳定表达后其集落形成能力的抑制有关。我们进一步测试了EZH 2是否可以抑制生长抑制p27基因，如胰腺癌所报道的那样。然而，结肠癌细胞系和结肠癌活检组织的表达分析没有揭示EZH 2和p27水平之间的一致相关性。此外，EZH 2耗竭不会重新诱导结肠癌细胞中的p27表达，表明EZH 2对p27的抑制可能是细胞或组织特异性的。全基因组转录组分析鉴定了结肠癌细胞系中受EZH 2耗尽影响的细胞基因。它们包括与细胞增殖或侵袭相关的几个癌症相关基因，如Dag 1，MageD 1，SDC 1，Timp 2和Tob 1。总之，我们的结果表明EZH 2耗尽阻断结肠癌细胞的生长。这些发现可能为结肠癌的治疗提供益处。
The Enhancer of Zeste 2 (EZH2) protein has been reported to stimulate cell growth in some cancers and is therefore considered to represent an interesting new target for therapeutic intervention. Here, we investigated a possible role of EZH2 for the growth control of colon cancer cells. RNA interference (RNAi)-mediated intracellular EZH2 depletion led to cell cycle arrest of colon carcinoma cells at the G1/S transition. This was associated with a reduction of cell numbers upon transient transfection of synthetic EZH2-targeting siRNAs and with inhibition of their colony formation capacity upon stable expression of vector-borne siRNAs. We furthermore tested whether EZH2 may repress the growth-inhibitory p27 gene, as reported for pancreatic cancer. However, expression analyses of colon cancer cell lines and colon cancer biopsies did not reveal a consistent correlation between EZH2 and p27 levels. Moreover, EZH2 depletion did not re-induce p27 expression in colon cancer cells, indicating that p27 repression by EZH2 may be cell- or tissue-specific. Whole genome transcriptome analyses identified cellular genes affected by EZH2 depletion in colon cancer cell lines. They included several cancer-associated genes linked to cellular proliferation or invasion, such as Dag1, MageD1, SDC1, Timp2, and Tob1. In conclusion, our results demonstrate that EZH2 depletion blocks the growth of colon cancer cells. These findings might provide benefits for the treatment of colon cancer.
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影响因子：
6
作者：
Fujita, Takeo;Liu, Weijun;Wan, Yong
通讯作者：
Wan, Yong
影响因子：
4.7
作者：
Kodach LL;Jacobs RJ;Heijmans J;van Noesel CJ;Langers AM;Verspaget HW;Hommes DW;Offerhaus GJ;van den Brink GR;Hardwick JC
通讯作者：
Hardwick JC
影响因子：
2.9
作者：
CHOMCZYNSKI, P;SACCHI, N
通讯作者：
SACCHI, N
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
8
作者：
Butz, K;Ristriani, T;Hoppe-Seyler, F
通讯作者：
Hoppe-Seyler, F