HOPX hypermethylation promotes metastasis via activating SNAIL transcription in nasopharyngeal carcinoma.
HOPX hypermethylation promotes metastasis via activating SNAIL transcription in nasopharyngeal carcinoma.
复制标题
HOPX 高甲基化通过激活鼻咽癌中的 SNAIL 转录促进转移。
DOI：
10.1038/ncomms14053
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发表时间：
2017-02-01
影响因子：
16.6
通讯作者：
Ma J
中科院分区：
文献类型：
--
作者：
Ren X;Yang X;Cheng B;Chen X;Zhang T;He Q;Li B;Li Y;Tang X;Wen X;Zhong Q;Kang T;Zeng M;Liu N;Ma J
鼻咽癌具有局部侵袭率高、早期远处转移等特点。越来越多的证据表明，表观遗传学异常在鼻咽癌的发生发展中起着重要作用。然而，鼻咽癌转移的表观遗传学机制仍不清楚。在这里，我们研究了鼻咽癌组织中异常甲基化的转录因子，我们发现HOP同源盒HOPX是最显著的高甲基化基因。我们一致地发现，HOXP在鼻咽癌组织和鼻咽癌细胞系中的表达下调。恢复HOPX的表达可抑制鼻咽癌细胞的转移并增强其对化疗的敏感性。这些作用是通过HOPX介导的表观遗传沉默蜗牛转录，通过增强蜗牛启动子中的组蛋白H3K9去乙酰化来介导的。此外，我们发现HOPX高甲基化水平的患者在培训和验证队列中都表现出较差的临床结果。综上所述，HOPX通过对蜗牛转录的表观遗传调控发挥肿瘤抑制作用，为鼻咽癌转移提供了一种新的预后生物标志物，也为鼻咽癌的治疗提供了靶点。HOPX是一种转录因子，在几种癌症中表观遗传沉默。在这里，作者通过分析甲基化特征，确定HOPX是鼻咽癌转移的抑制因子：HOPX通过去乙酰化介导的沉默机制抑制蜗牛的转录。
Nasopharyngeal carcinoma (NPC) is characterized by a high rate of local invasion and early distant metastasis. Increasing evidence indicates that epigenetic abnormalities play important roles in NPC development. However, the epigenetic mechanisms underlying NPC metastasis remain unclear. Here we investigate aberrantly methylated transcription factors in NPC tissues, and we identify the HOP homeobox HOPX as the most significantly hypermethylated gene. Consistently, we find that HOXP expression is downregulated in NPC tissues and NPC cell lines. Restoring HOPX expression suppresses metastasis and enhances chemosensitivity of NPC cells. These effects are mediated by HOPX-mediated epigenetic silencing of SNAIL transcription through the enhancement of histone H3K9 deacetylation in the SNAIL promoter. Moreover, we find that patients with high methylation levels of HOPX exhibit poor clinical outcomes in both the training and validation cohorts. In summary, HOPX acts as a tumour suppressor via the epigenetic regulation of SNAIL transcription, which provides a novel prognostic biomarker for NPC metastasis and therapeutic target for NPC treatment. HOPX is a transcription factor epigenetically silenced in several cancers. Here the authors, by analysing methylation profiles, identify HOPX as a suppressor of metastasis in nasopharyngeal carcinoma: mechanistically HOPX inhibits SNAIL transcription through deacetylation-mediated silencing.