Downregulation of HP1α suppresses proliferation of cholangiocarcinoma by restoring SFRP1 expression.
Downregulation of HP1α suppresses proliferation of cholangiocarcinoma by restoring SFRP1 expression.
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HP1α下调通过恢复SFRP1表达抑制胆管癌的增殖
DOI：
10.18632/oncotarget.10371
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发表时间：
2016-07-26
期刊：
影响因子：
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通讯作者：
Chen YJ
中科院分区：
文献类型：
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作者：
Cheng W;Tian L;Wang B;Qi Y;Huang W;Li H;Chen YJ
异染色质蛋白 1α (HP1α) 是一种介导染色质构象、基因沉默和癌症进展的基因。然而，关于 HP1α 在胆管癌 (CCA) 发病机制中的影响知之甚少。在本研究中，我们证明 HP1α 在 CCA 组织和细胞系中显着上调，而 HP1α 下调则导致细胞增殖受到抑制。然后我们发现下调HP1α可以降低分泌型卷曲相关蛋白1（SFRP1）启动子的H3K9me3富集度和DNA甲基化率，从而恢复SFRP1的表达。此外，恢复SFRP1表达可以抑制CCA细胞增殖。这些结果提供了对 HP1α 在 CCA 发病机制中的作用的机制理解，并可能为该疾病提供新的治疗靶点。
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.