title: Dicer promotes tumorigenesis by translocating to nucleus to promote SFRP1 promoter methylation in cholangiocarcinoma cells.
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.
authors.affiliation: Department of Biliary-Pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.|Department of Vascular Surgery, Wuxi People's Hospital, Nanjing Medical University, Wuxi, Jiangsu, China.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Cheng
authors.affiliation: Department of Biliary-Pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department of Biliary-Pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Li
authors.initials: L
authors.lastname: Tian
authors.affiliation: Department of Biliary-Pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Biliary-Pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Biliary-Pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D001650:Bile Duct Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000502:physiology; D018281:Cholangiocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics*; D021381:Protein Transport / Q000502:physiology; D043244:Ribonuclease III / Q000378:metabolism*; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone; D053487:DEAD-box RNA Helicases; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D043244:Ribonuclease III; C000715594:CBX5 protein, human; C117636:SFRP1 protein, human; D000094742:Secreted Frizzled-Related Proteins; C408087:DICER1 protein, human