Dicer promotes tumorigenesis by translocating to nucleus to promote SFRP1 promoter methylation in cholangiocarcinoma cells.
Dicer promotes tumorigenesis by translocating to nucleus to promote SFRP1 promoter methylation in cholangiocarcinoma cells.
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Dicer 通过易位到细胞核促进胆管癌细胞中 SFRP1 启动子甲基化来促进肿瘤发生
DOI：
10.1038/cddis.2017.57
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发表时间：
2017-02-23
影响因子：
9
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Cheng W;Qi Y;Tian L;Wang B;Huang W;Chen Y
作为核糖核酸酶RNaseIII家族的一员，迪格尔在调节哺乳动物癌细胞中CpG岛的甲基化方面发挥着重要作用。然而，潜在的行动机制仍不清楚。在这项研究中，我们证明了胆管癌细胞中DICER的上调及其与异染色质蛋白1α(Hp1α)相互作用的核移位。核DICER/HP1DNA复合体似乎促进了H3K9的三甲基化和分泌的卷曲相关蛋白1(α)启动子的DNA甲基化。DICER与SFRP1的表达呈负相关，可能通过抑制SFRP1促进CCA细胞的增殖和侵袭。肿瘤组织中的高表达与较大的肿瘤大小(>；3 cm)和淋巴结转移显著相关。我们的发现有助于在CCA的背景下描述DICER在表观遗传调控和肿瘤发生中的作用。
Dicer, a member of the RNase III family of endoribonucleases, has an important role in regulating methylation of CpG islands in mammal cancer cells. However, the underlying mechanism of action remains unclear. In this study, we demonstrated that upregulation of Dicer in cholangiocarcinoma (CCA) cells and its translocation to nuclues to interact with heterochromatin protein 1α (HP1α). The nuclear Dicer/HP1α complex appeared to promote both H3K9 trimethylation and DNA methylation of the secreted frizzled-related protein 1 (SFRP1) promoter. The expression of Dicer negatively correlated with that of SFRP1 and it appeared to promote CCA cell proliferation and invasion through repression of SFRP1 gene. High expression of Dicer in tumor tissues was significantly associated with larger tumor size (> 3 cm) and lymph node metastasis. Our findings help characterize the role of Dicer in epigenetic regulation and tumorigenesis in the context of CCA.