Down-regulation of VEZT gene expression in human gastric cancer involves promoter methylation and miR-43c

MicroRNAs (miRNAs) and promoter methylation are two vital important mechanisms for transcriptional inactivation of a gene in human cancer; VEZT gene is a plasma membrane component of adherens junctions, the role of VEZT still remains largely unexplored in gastric cancer. In the study, we analyzed the expression of VEZT gene in 30 pair matched gastric neoplastic and adjacent non-neoplastic tissues by quantitative real-time PCR, and we show that VEZT mRNA expression was significantly reduced in 30 pairs of gastric cancer specimens compared to matched normal gastric tissues. Methylation specific-PCR (MSP) and bisulfite sequence-PCR (BSP) methods showed hypermethylation status of promoter site of all gastric cancer cell lines. After DNA methylation inhibitor 5-Aza-2-deoxycytidine (5-Aza-CdR) treatment on gastric cancer cell lines, the gene protein level was improved and suppresses cell cycle progression remarkably. Furthermore, a luciferase reporter assay demonstrates that miR-43c directly targets adherens junctions' transmembrane protein (VEZT) and suppresses VEZT protein expression. These findings help clarify the molecular mechanisms involved in gastric cancer and indicate that VEZT gene may be a bona fide methylation-based treatment of gastric cancer. Crown Copyright (C) 2010 Published by Elsevier Inc. All rights reserved.