Candidate tumor suppressor ZNF154 suppresses invasion and metastasis in NPC by inhibiting the EMT via Wnt/β-catenin signalling.
Candidate tumor suppressor ZNF154 suppresses invasion and metastasis in NPC by inhibiting the EMT via Wnt/β-catenin signalling.
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候选肿瘤抑制因子 ZNF154 通过 Wnt/β-catenin 信号传导抑制 EMT，从而抑制 NPC 的侵袭和转移
DOI：
10.18632/oncotarget.20479
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发表时间：
2017-10-17
期刊：
影响因子：
--
通讯作者：
Jiang W
中科院分区：
文献类型：
--
作者：
Hu Y;Qi MF;Xu QL;Kong XY;Cai R;Chen QQ;Tang HY;Jiang W
鼻咽癌（NPC）在东南亚和中国南部尤为普遍，但其分子机制尚不清楚。DNA甲基化与肿瘤的发生和发展有关，包括鼻咽癌。通过全基因组DNA甲基化筛选方法，我们发现了ZNF154，但尚未研究其甲基化状态及其在NPC中的作用。采用甲基化特异性pcr （methylation specific-PCR， MSP）和定量序列阵列（Quantitative Sequenom MassARRAY）检测ZNF154在鼻咽癌中的甲基化状态。入侵和迁移能力通过伤口愈合和跨井入侵试验来检验。通过体内转移实验，明确了ZNF154在鼻咽癌转移中的作用。Western blotting分析ZNF154过表达后的蛋白变化。Kaplan-Meier分析确定ZNF154甲基化与鼻咽癌预后之间的关系。与永生化的鼻咽癌组织和细胞相比，由于启动子甲基化，ZNF154在鼻咽癌组织和细胞系中的表达经常下调。5-Aza -2-脱氧胞苷（5-Aza）去甲基化处理恢复了ZNF154在鼻咽癌细胞系中的表达。ZNF154在鼻咽癌细胞中的异位过表达抑制了细胞的体外迁移和侵袭以及体内肿瘤转移试验中肺结节的形成。机制研究表明，ZNF154抑制Wnt/β-catenin信号通路激活并阻止鼻咽癌的EMT。此外，Kaplan-Meier分析显示，在局部区域晚期鼻咽癌患者中，ZNF154启动子的高甲基化与较差的无病生存率（P = 0.032）和远端无转移生存率（P = 0.040）显著相关。综上所述，这些发现确定了ZNF154在NPC中作为肿瘤抑制因子的新作用。
Nasopharyngeal carcinoma (NPC) is especially prevalent in southeast Asia and southern China, but its molecular mechanisms remain poorly characterized. DNA methylation is associated with initiation and progression of tumors, including NPC. Through a genome-wide DNA methylation screening approach, we discovered ZNF154, but its methylation status and roles in NPC have not been investigated. The methylation status of ZNF154 in NPC was detected with Methylation specific-PCR (MSP) and Quantitative Sequenom MassARRAY. The invasion and migration capacities were examined by wound healing and transwell invasion assays. The role of ZNF154 in NPC metastasis was clarified with experimental metastasis assay in vivo. Western blotting analysis was used to investigate protein changes followed by ZNF154 over-expression. Kaplan-Meier analysis was performed to determine the association between ZNF154 methylation and prognosis in NPC. Compared to immortalized nasopharyngeal tissues and cells, ZNF154 expression was frequently downregulated in NPC tissues and cell lines due to promoter methylation. Demethylation treatment with 5-aza-2-deoxycytidine (5-Aza) restored ZNF154 expression in NPC cell lines. Ectopic overexpression of ZNF154 in NPC cells inhibited cell migration and invasion in vitro and lung nodule formation in an in vivo tumor metastasis assay. Mechanistic investigations suggested ZNF154 inhibits Wnt/β-catenin signalling pathway activation and prevents the EMT in NPC. Furthermore, Kaplan-Meier analysis showed hypermethylation of the ZNF154 promoter was associated with significantly poorer disease-free survival (P = 0.032) and distant metastasis-free survival (P = 0.040) among patients with locoregionally advanced NPC. Taken together, these findings define a novel role for ZNF154 as a tumor suppressor in NPC.
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影响因子：
12.3
作者：
Urrutia R
通讯作者：
Urrutia R
一种新型 19q13 核仁锌指蛋白通过抑制核糖体生物发生和诱导细胞凋亡来抑制肿瘤细胞生长，但在多种癌症中经常被沉默
影响因子：
5.2
作者：
Cheng, Yingduan;Liang, Pei;Tao, Qian
通讯作者：
Tao, Qian
影响因子：
51.1
作者：
Chen, Lei;Hu, Chao-Su;Ma, Jun
通讯作者：
Ma, Jun
影响因子：
11.2
作者：
Cheng, Yingduan;Geng, Hua;Tao, Qian
通讯作者：
Tao, Qian
影响因子：
8
作者：
Cowger, J. J. M.;Zhao, Q.;Torchia, J.
通讯作者：
Torchia, J.