Downregulation of HP1α suppresses proliferation of cholangiocarcinoma by restoring SFRP1 expression

Oncotarget. 2016 Jul 26;7(30):48107-48119. doi: 10.18632/oncotarget.10371.

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.

Keywords: DNA methylation; HP1α; SFRP1; cholangiocarcinoma; proliferation.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • Cholangiocarcinoma / genetics*
  • Cholangiocarcinoma / pathology
  • Chromobox Protein Homolog 5
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Down-Regulation
  • Female
  • Glycoproteins / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Middle Aged
  • Transfection

Substances

  • CBX5 protein, human
  • Chromosomal Proteins, Non-Histone
  • Glycoproteins
  • Intracellular Signaling Peptides and Proteins
  • WD repeat containing planar cell polarity effector
  • Chromobox Protein Homolog 5