Frequent silencing of popeye domain-containing genes, BVES and POPDC3, is associated with promoter hypermethylation in gastric cancer

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Title
Frequent silencing of popeye domain-containing genes, BVES and POPDC3, is associated with promoter hypermethylation in gastric cancer
Author(s)
Mirang Kim; H R Jang; Kee-Ok Ham; Tae-Wook Kang; Jeong Hwan KimSeon-Young Kim; S M Noh; K S Song; J S Cho; H Y Jeong; J C Kim; Hyang Sook Yoo; Yong Sung Kim
Bibliographic Citation
Carcinogenesis, vol. 31, no. 9, pp. 1685-1693
Publication Year
2010
Abstract
The Popeye domain-containing (POPDC) genes BVES, POPDC2 and POPDC3 encode proteins that regulate cell-cell adhesion and cell migration during development. Herein, we report the frequent downregulation of BVES and POPDC3 by promoter hypermethylation in gastric cancer. POPDC expression in 11 gastric cancer cell lines and 96 paired gastric tumor and normal adjacent tissues was analyzed with quantitative reverse transcription-polymerase chain reaction. The methylation status of BVES and POPDC3 was analyzed with methylated DNA immunoprecipitation sequencing, bisulfite sequencing and pyrosequencing. Expression of BVES and POPDC3 was downregulated in 73% of the gastric cancer cell lines and in 69% (BVES) and 87% (POPDC3) of the gastric cancer tissues. The BVES and POPDC3 promoter regions were hypermethylated in the gastric cancer cell lines in which they were silenced. Combined treatment with a DNA methylation inhibitor and a histone deacetylase inhibitor strongly induced BVES and POPDC3 expression. BVES and POPDC3 were hypermethylated in 69% (BVES) and 64% (POPDC3) of the gastric cancer tissues. We knocked down POPDC3 expression with short hairpin RNAs and examined the consequences on cell migration and invasion. Knockdown of POPDC3 in SNU-216 cells caused increased cell migration and invasion. Thus, epigenetic inactivation of BVES and POPDC3 occurs frequently in gastric tumors and may promote gastric cancer cell migration and invasion.
ISSN
0143-3334
Publisher
Oxford Univ Press
DOI
http://dx.doi.org/10.1093/carcin/bgq144
Type
Article
Appears in Collections:
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
Korea Bioinformation Center > 1. Journal Articles
Division of Biomedical Research > Genome Editing Research Center > 1. Journal Articles
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