Downregulation of HP1α suppresses proliferation of cholangiocarcinoma by restoring SFRP1 expression
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Wenlong Cheng1,*, Li Tian2,*, Bing Wang1, Yongqiang Qi1, Wenhua Huang1, Hongbo Li3, Yong-Jun Chen1
1Department of Biliary-Pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
2Department of Wuhan Medical Care Center for Women and Children, Wuhan, Hubei Province, China
3Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui Province, China
*These authors contributed equally to this work
Yong-Jun Chen, email: [email protected]
Keywords: HP1α, cholangiocarcinoma, proliferation, SFRP1, DNA methylation
Received: January 26, 2016 Accepted: June 12, 2016 Published: July 01, 2016
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.
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