Department of Pathophysiology, College of Basic Medical, Lanzhou University, Lanzhou 730020, Gansu Province, China.
Lanzhou General Hospital of Lanzhou Military Command of PLA, Lanzhou 730050, Gansu Province, China.
Biochem Biophys Res Commun. 2014 Feb 7;444(2):147-52. doi: 10.1016/j.bbrc.2014.01.012. Epub 2014 Jan 14.
Hypermethylation has been shown in the promoter region of the thyroid hormone receptor β1 (TRβ1) gene in several human tumors. However, its role in gastric cancer formation is still unclear. In the study, we analyzed mRNA expression of TRβ1 gene using real-time quantitative PCR (qPCR). A quantitative methylation-specific PCR (Q-MSP) assay was used to determine the methylation status of the TRβ1 gene promoter region in 46 pair-matched gastric neoplastic and adjacent non-neoplastic tissues. The results showed that TRβ1 mRNA expression was significantly reduced in gastric cancer specimens. The methylation of promoter of TRβ1 gene in gastric cancer tissues was significantly higher than in adjacent normal tissues. Promoter hypermethylation of the TRβ1 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 TRβ1 mRNA was increased in MKN-45, MKN-28, SGC-7901, but not increased in NCI-N87 and SNU-1. These results suggest that the TRβ1 gene plays important roles in the development of gastric cancer partially through epigenetic mechanisms.
甲状腺激素受体 β1（TRβ1）基因在多个人类肿瘤的启动子区域中存在超甲基化。然而，其在胃癌形成中的作用尚不清楚。在本研究中，我们使用实时定量 PCR（qPCR）分析了 TRβ1 基因的 mRNA 表达。使用定量甲基化特异性 PCR（Q-MSP）测定法检测了 46 对配对的胃癌和相邻非肿瘤组织中 TRβ1 基因启动子区域的甲基化状态。结果表明，胃癌标本中 TRβ1 mRNA 表达显著降低。胃癌组织中 TRβ1 基因启动子的甲基化明显高于相邻正常组织。TRβ1 基因启动子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-氮杂-2-脱氧胞苷（5-Aza-dC）处理胃癌细胞系 MKN-45、MKN-28、SGC-7901、NCI-N87 和 SNU-1。结果表明，在 MKN-45、MKN-28、SGC-7901 中 TRβ1 mRNA 的表达增加，但在 NCI-N87 和 SNU-1 中未增加。这些结果表明，TRβ1 基因通过表观遗传机制在胃癌的发生发展中起重要作用。
