VEZT, a novel putative tumor suppressor, suppresses the growth and tumorigenicity of gastric cancer.
Vezatin (VEZT), an adherens junctions transmembrane protein, was identified as a putative tumor suppressor in our previous study. However, the role of VEZT in tumorigenesis remains elusive. We aimed to clarify its epigenetic regulation and biological functions in gastric cancer. In this study, we show that the expression level of VEZT is involved in lymphatic metastasis, depth of cancer invasion and TNM stage in 104 gastric cancer patients. Bisulfate sequencing polymerase chain reaction (BSP) methods showed that VEZT was hypermethylated in tissues and corresponding blood of gastric cancer patients compared with healthy controls. Helicobacter pylori (H. pylori) infection induces the methylation and silencing of VEZT in GES-1 cells. Restoring VEZT expression in MKN-45 and NCI-N87 gastric cancer cells inhibited growth, invasion and tumorigenesis in vitro and in vivo. Global microarray analysis was applied to analyze the molecular basis of the biological functions of VEZT after VEZT transfection combined with real-time PCR and chromatin immunoprecipitation assay. G protein-coupled receptor 56(GPR56), cell growth, cell division cycle 42(CDC42), migration/invasion and transcription factor 19(TCF19), cell cycle progression, were identified as direct VEZT target genes. TCF19, a novel target of VEZT, was functionally validated. Overexpression of TCF19 in MKN-45 cells increased cell cycle progress and growth ability. This study provides novel insight into the regulation of the VEZT gene, which could represent a potential target for therapeutic anti-cancer strategies.
Department of Gastrointestinal Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
Ruizhen
R
Miao
Xiaobo
X
Guo
Qiaoming
Q
Zhi
Yulong
Y
Shi
Leping
L
Li
Xuehui
X
Mao
Li
L
Zhang
Chensheng
C
Li
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D016000:Cluster Analysis; D019175:DNA Methylation; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D016481:Helicobacter Infections / Q000235:genetics; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D015203:Reproducibility of Results; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D047368:Tumor Burden; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D002352:Carrier Proteins; D008565:Membrane Proteins; C098583:TCF19 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C494547:VEZT protein, human