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MUC1 is associated with TFF2 methylation in gastric cancer.

Abstract：

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.

journal_name

Clin Epigenetics

journal_title

Clinical epigenetics

authors

Ge Y,Ma G,Liu H,Lin Y,Zhang G,Du M,Wang M,Chu H,Zhang H,Zhang Z

doi

10.1186/s13148-020-00832-6

subject

Has Abstract

pub_date

2020-03-02 00:00:00

pages

37

issue

1

eissn

1868-7075

issn

1868-7083

pii

10.1186/s13148-020-00832-6

journal_volume

12

pub_type

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