Dicer promotes tumorigenesis by translocating to nucleus to promote SFRP1 promoter methylation in cholangiocarcinoma cells

被引：22

作者：

Cheng, Wenlong ^{[1
,2
]}

Qi, Yongqiang ^{[1
]}

Tian, Li ^{[1
]}

Wang, Bing ^{[1
]}

Huang, Wenhua ^{[1
]}

Chen, Yongjun ^{[1
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Biliary Pancreat Surg, Wuhan 430000, Hubei, Peoples R China

[2] Nanjing Med Univ, Wuxi Peoples Hosp, Dept Vasc Surg, Wuxi, Jiangsu, Peoples R China

来源：

CELL DEATH & DISEASE | 2017年 / 8卷

基金：

中国国家自然科学基金;

关键词：

WNT ANTAGONIST SFRP1; CANCER; RNA; MICRORNA; EXPRESSION; HETEROCHROMATIN; REQUIREMENT; PROTEINS; PATHWAY; GENE;

D O I：

10.1038/cddis.2017.57

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 1 alpha (HP1 alpha). The nuclear Dicer/HP1 alpha 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.

引用

页码：e2628 / e2628

页数：9

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