Down-regulation Of HP1α Expression Suppresses Cholangiocarcinoma Proliferation By Restoring SFRP1 Expression Associated With Chromatin Modifications

Objective To investigate the role and molecular mechanism of HP1α in cholangiocarcinoma(CCA), and offer a novel therapeutic target in this disease.Methods We performed Immunohistochemistry, Western blot and real-time PCR to detect the HP1α expression of CCA tissues and cells. We stably changed HP1α expression through transfecting lentivirus carrying HP1α, small interfering RNA(si RNA) of HP1α and negative control vector, named LV-HP1α, LV-si R-HP1α and NC, respectively. Cell proliferation assays, cell migration and invasion assays were performed to observe the biological behavior of CCA cells. To investigate the molecular mechanism of HP1α in CCA, we carried out Co-immunoprecipitation, Chromatin immunoprecipitation and Bisulfite sequencing PCR to test the status of chromatin modifications in secreted frizzled-related protein 1(SFRP1) promoter.Results In this study, we demonstrated that HP1α is significantly up-regulated in CCA tissues and cell lines, and down-regulation of HP1α can significantly suppress cell proliferation. We subsequently found that down-regulation of HP1α can reduce the H3K9me3 enrichment and the Cp Gs methylation rate of SFRP1 promoter, resulting in restoring the expression of SFRP1. The restoration of SFRP1 expression can supress CCA cells proliferation.Conclutions Down-regulation of HP1α inhibits CCA cell proliferation through restoring SFRP1 expression associated with chromatin modifications.