Hypermethylation of SHISA3 Promotes Nasopharyngeal Carcinoma Metastasis by Reducing SGSM1 Stability
Hypermethylation of SHISA3 Promotes Nasopharyngeal Carcinoma Metastasis by Reducing SGSM1 Stability
复制标题
SHISA3的高甲基化通过降低SGSM1稳定性促进鼻咽癌转移
DOI：
10.1158/0008-5472.can-18-1754
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发表时间：
2019
期刊：
影响因子：
11.2
通讯作者：
Liu Na
中科院分区：
文献类型：
--
作者：
Zhang Jian;Li Ying-Qin;Guo Rui;Wang Ya-Qin;Zhang Pan-Pan;Tang Xin-Ran;Wen Xin;Hong Xiao-Hong;Lei Yuan;He Qing-Mei;Yang Xiao-Jing;Sun Ying;Ma Jun;Liu Na
DNA甲基化改变是癌症的一个重要特征，异常甲基化在鼻咽癌（NPC）的发生发展中具有重要意义。然而，NPC转移的甲基化机制仍不清楚。分析公共数据库的数据并进行我们自己的实验，我们在这里报告SHISA 3的启动子高甲基化是常见的，并有助于该基因在许多类型的肿瘤中的下调，SHISA 3通过阻断E3泛素连接酶三联体21（TRIM 21）介导的泛素化和降解小G蛋白信号调节因子1（SGSM 1）抑制鼻咽癌细胞体外和体内侵袭和转移以及通过抑制MAPK通路的活化。沉默SGSM 1可解除SHISA 3对鼻咽癌细胞迁移和侵袭的抑制作用。新发现的SHISA 3-TRIM 21-SGSM 1轴可能成为NPC的新治疗靶点。重要意义这些发现强调了新发现的肿瘤抑制因子SHISA 3抑制鼻咽癌侵袭和转移的机制。
Altered DNA methylation is a key feature of cancer, and aberrant methylation is important in nasopharyngeal carcinoma (NPC) development. However, the methylation mechanisms underlying metastasis of NPC remain unclear. Analyzing data from public databases and conducting our own experiments, we report here that promoter hypermethylation ofSHISA3is common and contributes to the downregulation of this gene in many types of tumors, including NPC.SHISA3suppressed NPC cell invasion and metastasisin vitroandin vivoby impeding the E3 ubiquitin ligase tripartite motif containing 21 (TRIM21)–mediated ubiquitination and degradation small G protein signaling modulator 1 (SGSM1) and by inhibiting the MAPK pathway activation. SilencingSGSM1abrogated the inhibitory effect ofSHISA3on NPC cell migration and invasion. This newly identifiedSHISA3–TRIM21–SGSM1axis could be a novel therapeutic target in NPC.SignificanceThese findings highlight the mechanism by which a newly identified tumor suppressor SHISA3 suppresses invasion and metastasis of nasopharyngeal carcinoma.