title: Downregulation of HP1α suppresses proliferation of cholangiocarcinoma by restoring SFRP1 expression.
abstract: Heterochromatin protein 1α (HP1α) is a gene that mediates chromatin conformation, gene silencing and cancer progression. However, little is known regarding the impact of HP1α in the pathogenesis of cholangiocarcinoma (CCA). In the present study, we demonstrate that HP1α is significantly upregulated in CCA tissues and cell lines, while downregulation of HP1α leads to suppression of cell proliferation. Then we find that downregulation of HP1α can decrease H3K9me3 enrichment and DNA methylation rate of secreted frizzled-related protein 1 (SFRP1) promoter, resulting in restoring the expression of SFRP1. Moreover, restoration of SFRP1 expression can suppress CCA cells proliferation. These results provide a mechanistic understanding of the role of HP1α in the pathogenesis of CCA and may offer a novel therapeutic target in this disease.
authors.affiliation: Department of Biliary-Pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Cheng
authors.affiliation: Department of Wuhan Medical Care Center for Women and Children, Wuhan, Hubei Province, 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 Province, 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 Province, 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 Province, China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui Province, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Biliary-Pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Chen
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000473:pathology; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D014162:Transfection; D000099274:Frizzled-Related Proteins
chemical_list: D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D000099274:Frizzled-Related Proteins; C000715594:CBX5 protein, human
keywords: DNA methylation; HP1α; SFRP1; cholangiocarcinoma; proliferation