TIPE3 hypermethylation correlates with worse prognosis and promotes tumor progression in nasopharyngeal carcinoma.
TIPE3 hypermethylation correlates with worse prognosis and promotes tumor progression in nasopharyngeal carcinoma.
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TIPE3 高甲基化与较差的预后相关，并促进鼻咽癌的肿瘤进展。
DOI：
10.1186/s13046-018-0881-5
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发表时间：
2018-09-14
期刊：
影响因子：
--
通讯作者：
Liu N
中科院分区：
文献类型：
--
作者：
Ren XY;Wen X;Li YQ;Zhang J;He QM;Yang XJ;Tang XR;Wang YQ;Zhang PP;Chen XZ;Cheng B;Ma J;Liu N
越来越多的证据表明，DNA甲基化异常在癌症发展中起着关键作用。我们先前的全基因组甲基化图谱显示肿瘤坏死因子α诱导蛋白8样3（TIPE 3）在鼻咽癌（NPC）中高甲基化。然而，TIPE 3甲基化与其mRNA表达的关系以及其在NPC中的生物学作用尚不清楚。进行亚硫酸氢盐焦磷酸测序和定量RT-PCR以定量TIPE 3甲基化和表达水平。Kaplan-Meier曲线和考克斯回归分析用于估计从两家医院收集的两个患者队列（n = 441）中TIPE 3甲基化水平与存活率之间的相关性。采用MTT法、集落形成实验、Transwell迁移侵袭实验、裸鼠移植瘤生长模型和肺转移模型研究TIPE 3对鼻咽癌细胞的作用。我们发现TIPE 3 CpG岛（CGI）在包括NPC在内的许多癌症中高度甲基化，其mRNA水平下调。TIPE 3下调与其CGI高甲基化相关。此外，具有高TIPE 3 CGI甲基化水平的NPC患者的临床结果比具有低甲基化水平的患者差。TIPE 3 CGI甲基化水平是独立的预后因素。此外，恢复TIPE 3表达在体外显著抑制NPC细胞增殖、迁移和侵袭，在体内抑制肿瘤生长和肺转移定植，而沉默TIPE 3则以相反的方式起作用。TIPE 3下调与几种实体癌中的CGI超甲基化相关。TIPE 3在NPC中作为肿瘤抑制因子，提供了对NPC进展的进一步了解，并代表了NPC的潜在预后生物标志物。本文的在线版本（10.1186/s13046-018-0881-5）包含补充材料，可供授权用户使用。
Increasing evidence recognizes that DNA methylation abnormalities play critical roles in cancer development. Our previous genome-wide methylation profile showed that tumor necrosis factor-alpha-induced protein 8 like 3 (TIPE3) was hypermethylated in nasopharyngeal carcinoma (NPC). However, the relationship between TIPE3 methylation and its mRNA expression, as well as its biological roles in NPC are unknown. Bisulfite pyrosequencing and quantitative RT-PCR were performed to quantify the TIPE3 methylation and expression levels. Kaplan-Meier curves and Cox regression analysis were used to estimate the correlation between TIPE3 methylation levels and survival in two patient cohorts collected from two hospitals (n = 441). The MTT, colony formation, Transwell migration and invasion assays, and xenograft tumor growth and lung metastatic colonization models were used to identify the functions of TIPE3 on NPC cells. We found that TIPE3 CpG island (CGI) was hypermethylated and its mRNA levels were downregulated in many cancers, including NPC. TIPE3 downregulation was associated with its CGI hypermethylation. Furthermore, NPC patients with high TIPE3 CGI methylation levels had poorer clinical outcomes than those with low methylation levels. The TIPE3 CGI methylation level was an independent prognostic factor. Moreover, restoring TIPE3 expression significantly inhibited NPC cell proliferation, migration and invasion in vitro, and suppressed tumor growth and lung metastatic colonization in vivo, while silencing TIPE3 acted in an opposite way. TIPE3 downregulation correlates with its CGI hypermethylation in several solid cancers. TIPE3 acts as a tumor suppressor in NPC, providing a further insight into NPC progression and representing a potential prognostic biomarker for NPC. The online version of this article (10.1186/s13046-018-0881-5) contains supplementary material, which is available to authorized users.
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DOI：
10.1007/978-1-61779-292-2_11
发表时间：
2012
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
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作者：
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Carninci, Piero
影响因子：
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作者：
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影响因子：
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作者：
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影响因子：
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