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.
Highlights
Cholangiocarcinoma (CCA) is a malignant tumor arising from bile duct epithelial cells
Using overexpression and knockdown studies, we demonstrated that Heterochromatin protein 1α (HP1α) silencing can restore the expression of secreted frizzled-related protein 1 (SFRP1) via chromatin modifications which subsequently suppresses cell proliferation
We revealed that downregulation of HP1α could reduce DNA methylation of the SFRP1 promoter (Figure 4G), we performed Western blot to evaluate the differences of SFRP1 expression between LV-NC and LV-siR-HP1α cells (Figure 5A)
Summary
Cholangiocarcinoma (CCA) is a malignant tumor arising from bile duct epithelial cells. Recent evidences suggest that HP1α can bind to euchromatin and dynamically participates in gene regulation [7,8,9], and in the context of cancer pathogenesis, a breast cancer study has shown correlations between alterations in HP1α protein levels and cancer progression [10]. Taken together, these results suggest that HP1α can contribute to tumor progression, the molecular mechanisms require further clarification
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