Piwil1 causes epigenetic alteration of PTEN gene via upregulation of DNA methyltransferase in type I endometrial cancer
Piwil1 causes epigenetic alteration of PTEN gene via upregulation of DNA methyltransferase in type I endometrial cancer
复制标题
Piwil1 通过上调 I 型子宫内膜癌中 DNA 甲基转移酶引起 PTEN 基因的表观遗传改变。
DOI：
10.1016/j.bbrc.2015.06.028
复制
发表时间：
2015-08-07
影响因子：
3.1
通讯作者：
Wan, Xiao-Ping
中科院分区：
文献类型：
--
作者：
Chen, Zheng;Che, Qi;Wan, Xiao-Ping
Piwil1是Piwi家族的一员，已经被很好地证明参与了与DNA高甲基化相关的肿瘤发生。据报道，Piwil1在包括子宫内膜癌在内的各种类型的癌症中都有过表达。然而，Piwil1在子宫内膜癌中的潜在机制仍很不清楚。PTEN在子宫内膜癌的发生过程中发挥重要的肿瘤抑制作用。本研究旨在探讨Piwil1是否能调节PTEN的表达。在此，我们发现Piwil1可以促进Ishikawa细胞PTEN表达的缺失，并增加PTEN基因启动子的异常甲基化。我们还发现，Piwil1可以调节DNA甲基转移酶1(DNMT1)的表达。沉默DNMT1基因可上调Ishikawa细胞中PTEN基因的表达，改变PTEN基因启动子的甲基化状态。这些结果表明，Piwil1通过DNMT1介导的PTEN高甲基化导致PTEN表达缺失。综上所述，这些数据提供了Piwil1在子宫内膜癌中的一种新的调控机制。(C)2015 Elsevier Inc.保留所有权利。
Piwil1, a member of the Piwi family, has been well demonstrated to mediate tumorigenesis associated with DNA hypermethylation. It has been reported that Piwil1 is overexpressed in various types of cancer, including endometrial cancer. However, the underlying mechanism of Piwil1 in endometrial cancer remains largely unclear. PTEN exerts an important tumor suppressor role in endometrial carcinogenesis. The present study aimed to investigate whether Piwil1 could regulate the expression of PTEN. Herein, we found that Piwil1 could promote the loss of PTEN expression and increase aberrant hypermethylation of PTEN gene promoter in Ishikawa cells. We also found that Piwil1 could regulate the expression of DNA methyltransferase 1 (DNMT1). Silencing DNMT1 gene could upregulate the PTEN gene expression and change the methylation status of PTEN gene promoter in Ishikawa cells. These results suggested that Piwil1 caused the loss of PTEN expression through DNMT1-mediated PTEN hypermethylation. Taken together, these data provide a novel regulatory mechanism of Piwil1 in endometrial cancer. (C) 2015 Elsevier Inc. All rights reserved.