Han Ting, Jiao Feng, Hu Hai, Yuan Cuncun, Wang Lei, Jin Zi-Liang, Song Wei-Feng, Wang Li-Wei
Department of Medical Oncology and Pancreatic Cancer Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China.
Shanghai Key Laboratory of Pancreatic Diseases, Shanghai 201620, China.
Oncotarget. 2016 Mar 8;7(10):11194-207. doi: 10.18632/oncotarget.7156.
Enhancer of zeste homolog 2 (EZH2) is an essential component of the polycomb repressive complex 2 (PRC2), which is required for epigenetic silencing of target genes, including those affecting cancer progression. Its role in pancreatic cancer remains to be clarified; therefore, we investigated the effects of aberrantly expressed EZH2 on pancreatic cancer. We found that EZH2 expression is up-regulated in pancreatic cancer tissues and positively correlated with lymph node metastasis and advanced clinical stage in pancreatic cancer patients. EZH2 knockdown in pancreatic cancer cell lines inhibited cell migration and invasion, but did not alter cell proliferation. Silencing of EZH2 also increased E-cadherin expression in vitro, and E-cadherin expression was inversely correlated with EZH2 expression in pancreatic cancer tissue samples. Patients with high EZH2 and low E-cadherin expression had the worst prognosis. RIP and ChIP assays suggest that EZH2 is recruited to the E-cadherin promoter by the long non-coding RNA, MALAT-1 (metastasis associated in lung adenocarcinoma transcript 1), where it represses E-cadherin expression. Our results show that EZH2-based therapies may be an option for the treatment of pancreatic cancer.
zeste 同源物 2 增强子（EZH2）是多梳抑制复合物 2（PRC2）的重要组成部分，该复合物对于包括那些影响癌症进展的靶基因的表观遗传沉默是必需的。其在胰腺癌中的作用仍有待阐明；因此，我们研究了异常表达的 EZH2 对胰腺癌的影响。我们发现 EZH2 在胰腺癌组织中表达上调，并且与胰腺癌患者的淋巴结转移和临床晚期呈正相关。在胰腺癌细胞系中敲低 EZH2 可抑制细胞迁移和侵袭，但不改变细胞增殖。EZH2 的沉默在体外也增加了 E-钙黏蛋白的表达，并且在胰腺癌组织样本中 E-钙黏蛋白的表达与 EZH2 的表达呈负相关。EZH2 高表达和 E-钙黏蛋白低表达的患者预后最差。RNA 免疫沉淀（RIP）和染色质免疫沉淀（ChIP）分析表明，长链非编码 RNA MALAT-1（肺腺癌转移相关转录本 1）将 EZH2 招募至 E-钙黏蛋白启动子，在那里它抑制 E-钙黏蛋白的表达。我们的结果表明，基于 EZH2 的疗法可能是治疗胰腺癌的一种选择。
