Down-regulation of thyroid hormone receptor β1 gene expression in gastric cancer involves promoter methylation
Down-regulation of thyroid hormone receptor β1 gene expression in gastric cancer involves promoter methylation
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DOI：
10.1016/j.bbrc.2014.01.012
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发表时间：
2014-02-07
影响因子：
3.1
通讯作者：
Li, Qing
中科院分区：
文献类型：
--
作者：
Ling, Yaqin;Shi, Xiangqun;Li, Qing
在几种人类肿瘤中，甲状腺激素受体β 1 （TR β 1）基因的启动子区域显示出高甲基化。然而，其在胃癌形成中的作用尚不清楚。本研究采用实时定量PCR （real-time quantitative PCR, qPCR）分析了TR β 1基因的mRNA表达。采用定量甲基化特异性PCR （Q-M5P）测定46对配对的胃肿瘤和邻近非肿瘤组织中TR β 1基因启动子区域的甲基化状态。结果显示，胃癌标本中TR β 1 mRNA表达明显降低。胃癌组织中TR β 1基因启动子甲基化水平明显高于癌旁正常组织。启动子TRIM基因的高甲基化与肿瘤浸润、淋巴结转移和远处转移相关，但与其他临床病理特征无关。我们用5- aza -2-脱氧胞苷（5-Aza-dC）处理胃癌细胞株MKN-45、MKN-28、SGC-7901、NCI-N87和scn -1。结果显示，TR β 1 mRNA在MKN-45、MKN-28、SGC-7901中表达升高，而在NCI-N87和scn -1中表达不升高。这些结果表明，TR β 1基因在胃癌的发生发展中部分通过表观遗传机制发挥重要作用。(C) 2014爱思唯尔公司版权所有。
Hypermethylation has been shown in the promoter region of the thyroid hormone receptor beta 1 (TR beta 1) gene in several human tumors. However, its role in gastric cancer formation is still unclear. In the study, we analyzed mRNA expression of TR beta 1 gene using real-time quantitative PCR (qPCR). A quantitative methylation-specific PCR (Q-M5P) assay was used to determine the methylation status of the TR beta 1 gene promoter region in 46 pair-matched gastric neoplastic and adjacent non-neoplastic tissues. The results showed that TR beta 1 mRNA expression was significantly reduced in gastric cancer specimens. The methylation of promoter of TR beta 1 gene in gastric cancer tissues was significantly higher than in adjacent normal tissues. Promoter hypermethylation of the TRIM gene correlated with tumor infiltration, lymph node metastasis, and distant metastasis, but it was not associated with other clinicopathological characteristics. We treated gastric cancer cell lines MKN-45, MKN-28, SGC-7901, NCI-N87, and SNU-1 with 5-Aza-2-deoxycytidine (5-Aza-dC). The results showed the expression of TR beta 1 mRNA was increased in MKN-45, MKN-28, SGC-7901, but not increased in NCI-N87 and SNU-1. These results suggest that the TR beta 1 gene plays important roles in the development of gastric cancer partially through epigenetic mechanisms. (C) 2014 Elsevier Inc. All rights reserved.