Yonsei Med J.  2021 Nov;62(11):1005-1015. 10.3349/ymj.2021.62.11.1005.

Regulation of MUC6 Methylation Correlates with Progression of Gastric Cancer

• Shi D
• Xi Xx

• KMID: 2521451
• DOI: http://doi.org/10.3349/ymj.2021.62.11.1005

Abstract

Purpose
This study aimed to investigate the mechanistic downregulation of mucin 6 (MUC6) and its influence on the progression of gastric cancer (GC).
Materials and Methods
The expression of MUC6 was examined in 40 GC patients. The methylation status of the MUC6 promoter region was investigated using GC cell lines and GC tissue specimens by immunohistochemistry and/or quantitative polymerase chain reaction (qPCR). MUC6 was knocked down in the gastric epithelial cells (GES-1) cell and overexpressed in the SGC7901 cell. The effects of MUC6 knockdown and overexpression on cell migration and invasion were examined using Transwell assays. The effects of demethylation and methylation on MUC6 expression were examined by western blot, qPCR, or double luciferase reporter assays.
Results
The expression of MUC6 in GC with lymph node metastasis and poor pathological stage was significantly lower than that in GC without lymph node metastasis and good pathological stage, respectively. While cell migration and invasion were significantly decreased after overexpression of MUC6, these abilities significantly increased after the knockdown of MUC6. The methylation levels of MUC6 in GC tissues and GC cell lines were significantly higher than those in para-cancerous tissues and normal GES. Promoter methylation could significantly reduce the binding of related transcription factors to the MUC6 promoter. The expression of MUC6 increased with the concentration and time of action of demethylation drugs.
Conclusion
Expression of MUC6 was regulated by promotor methylation. This methylation of the MUC6 promoter may lead to significant downregulation of MUC6 in GC and promote the progression of GC.

Keyword

MUC6; methylation; gastric cancer