BACKGROUND Emerging evidence has shown that MUC1 and TFF2 play crucial roles in the H. pylori-infected pathogenesis of gastric cancer (GC). A recent study revealed that H. pylori infection induced obviously increased Tff2 methylation levels in Muc1-/- mice compared with controls. However, little is known of the molecular mechanism on MUC1 regulating the expression of TFF2. METHODS We conducted a correlation analysis of MUC1 and TFF2 in public databases and our adjacent GC tissues. Besides, MUC1 overexpression vector or small interfering RNA (siRNA) was transfected into GC cells to assess the change in TFF2 expression. Furthermore, the methylation status of TFF2 was measured by bisulfite sequencing PCR (BSP). RESULTS The expression of MUC1 was significantly lower in non-cardia and cardia tumor tissues than that in normal tissues. Downregulation of TFF2 expression was also observed in GC tissues. In addition, we found that MUC1 expression was positively associated with TFF2 expression in GC tissues, especially among GC patients with H. pylori infection. Overexpression of MUC1 in BGC-823 and SGC-7901 cell lines substantially increased the TFF2 expression, whereas knockdown of MUC1 reverted this effect. Moreover, MUC1 was negatively related to the methylation of TFF2 in the co-expression analysis. The results of BSP experiments showed that compared with negative vector group, the methylation level of TFF2 was decreased in GC cells transfected with MUC1 overexpression vector. Additionally, survival analysis indicated that GC patients with lower level of MUC1 or TFF2 had a worse outcome. CONCLUSION Our results indicated that MUC1 was associated with the methylation of TFF2, which may have implications for TFF2 expression in GC. These findings warrant further research toward the underlying mechanism of MUC1 influenced the TFF2 methylation.

中文翻译：

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MUC1与胃癌中的TFF2甲基化有关。

背景技术新兴证据表明，MUC1和TFF2在幽门螺杆菌感染的胃癌（GC）发病机理中起关键作用。最近的一项研究表明，与对照组相比，幽门螺杆菌感染在Muc1-/-小鼠中诱导的Tff2甲基化水平明显升高。然而，关于MUC1调节TFF2表达的分子机制知之甚少。方法我们在公共数据库和邻近的GC组织中进行了MUC1和TFF2的相关性分析。此外，将MUC1过表达载体或小干扰RNA（siRNA）转染到GC细胞中以评估TFF2表达的变化。此外，通过亚硫酸氢盐测序PCR（BSP）测量了TFF2的甲基化状态。结果非UC门和and门肿瘤组织中MUC1的表达明显低于正常组织。在GC组织中也观察到TFF2表达的下调。此外，我们发现在胃癌组织中，尤其是在患有幽门螺杆菌感染的胃癌患者中，MUC1表达与TFF2表达正相关。BUC-823和SGC-7901细胞系中MUC1的过表达实质上增加了TFF2的表达，而MUC1的敲低则恢复了该作用。此外，在共表达分析中，MUC1与TFF2的甲基化呈负相关。BSP实验的结果表明，与阴性载体组相比，MUC1过表达载体转染的GC细胞中TFF2的甲基化水平降低。此外，生存分析表明，MUC1或TFF2水平较低的GC患者的预后较差。结论我们的结果表明MUC1与TFF2的甲基化有关，这可能对TFF2在GC中的表达有影响。这些发现需要进一步研究MUC1影响TFF2甲基化的潜在机制。