MUC1 is associated with TFF2 methylation in gastric cancer

Yuqiu Ge,Meilin Wang,Hanting Liu,Haiyan Chu,Mulong Du,Haiyan Zhang,Zhengdong Zhang,Gaoxiang Ma,Gang Zhang,Yadi Lin

doi:10.1186/s13148-020-00832-6

Abstract

BackgroundEmerging 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.MethodsWe 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).ResultsThe 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.ConclusionOur 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.

Highlights

Emerging evidence has shown that Mucin 1 (MUC1) and Trefoil factor family 2 (TFF2) play crucial roles in the H. pylori-infected pathogenesis of gastric cancer (GC)
It is noteworthy that previous genome-wide association studies (GWASs) have identified several risk loci located in MUC1 gene, which were significantly associated with the susceptibility of GC [12, 13]
Both MUC1 and TFF2 expression showed a slight decreased in cardia tissue compared with noncardia tumor tissue, but there were no significantly differences (Supplementary Figure 1)

Summary

Introduction

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 Tff methylation levels in Muc1−/− mice compared with controls. It has been established that H. pylori infection is the most important risk factor for GC [3]. Accumulating evidence has shown that eradication of H. pylori infection was significantly associated with the reduced incidence of GC, highlighting the pathogenic role of H. pylori in GC [4, 5]. It has been reported that MUC1 played a crucial role in H. pylori-associated gastritis through acting as a protective physical barrier against pathogens [8, 10]. It is noteworthy that previous genome-wide association studies (GWASs) have identified several risk loci located in MUC1 gene, which were significantly associated with the susceptibility of GC [12, 13]

Methods

Results

Conclusion