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

Wenlong Cheng; Yongqiang Qi; Li Tian; Bing Wang; Wenhua Huang; Yongjun Chen

doi:10.1038/cddis.2017.57

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

Cell Death Dis. 2017 Feb 23;8(2):e2628. doi: 10.1038/cddis.2017.57.

Authors

Wenlong Cheng^{1

2}, Yongqiang Qi¹, Li Tian¹, Bing Wang¹, Wenhua Huang¹, Yongjun Chen¹

Affiliations

¹ Department of Biliary-Pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
² Department of Vascular Surgery, Wuxi People's Hospital, Nanjing Medical University, Wuxi, Jiangsu, China.

Abstract

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.

MeSH terms

Animals
Bile Duct Neoplasms / genetics
Bile Duct Neoplasms / metabolism*
Bile Duct Neoplasms / pathology
Carcinogenesis / genetics
Carcinogenesis / metabolism*
Carcinogenesis / pathology
Cell Line
Cell Line, Tumor
Cell Nucleus / genetics
Cell Nucleus / metabolism*
Cell Proliferation / physiology
Cholangiocarcinoma / genetics
Cholangiocarcinoma / metabolism*
Cholangiocarcinoma / pathology
Chromobox Protein Homolog 5
Chromosomal Proteins, Non-Histone / metabolism
DEAD-box RNA Helicases / metabolism*
DNA Methylation / genetics*
Epigenesis, Genetic / genetics
HEK293 Cells
Humans
Intercellular Signaling Peptides and Proteins / metabolism*
Lymphatic Metastasis / genetics
Lymphatic Metastasis / pathology
Male
Membrane Proteins / metabolism*
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Invasiveness / genetics
Neoplasm Invasiveness / pathology
Promoter Regions, Genetic / genetics*
Protein Transport / physiology
Ribonuclease III / metabolism*

Substances

CBX5 protein, human
Chromosomal Proteins, Non-Histone
Intercellular Signaling Peptides and Proteins
Membrane Proteins
SFRP1 protein, human
Chromobox Protein Homolog 5
DICER1 protein, human
Ribonuclease III
DEAD-box RNA Helicases