Epigenetic silencing of BTB and CNC homology 2 and concerted promoter CpG methylation in gastric cancer

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Title
Epigenetic silencing of BTB and CNC homology 2 and concerted promoter CpG methylation in gastric cancer
Author(s)
Keeok Ham; Hee Jin Kim; K T Lee; Jeong Hwan KimMi Rang KimSeon-Young Kim; S M Noh; K S Song; Yong Sung Kim
Bibliographic Citation
Cancer Letters, vol. 351, no. 2, pp. 206-214
Publication Year
2014
Abstract
BTB and CNC homology 2 (BACH2) is a lymphoid-specific transcription factor with a prominent role in B-cell development. Genetic polymorphisms within a single locus encoding BACH2 are associated with various autoimmune diseases and allergies. In this study, restriction landmark genomic scanning revealed methylation at a NotI site in a CpG island covering the BACH2 promoter in gastric cancer cell lines and primary gastric tumors. Increased methylation of the BACH2 promoter was observed in 52% (43/83) of primary gastric tumors, and BACH2 hypermethylation was significantly associated with decreased gene expression. Treatment with 5-aza-2'-deoxycytidine and/or trichostatin. A restored BACH2 expression in BACH2-silenced gastric cancer cell lines, and knockdown of BACH2 using short hairpin RNA (i.e. RNA interference) increased cell proliferation in gastric cancer cells. Clinicopathologic data showed that decreased BACH2 expression occurred significantly more frequently in intestinal-type (27/44, 61%) compared with diffuse-type (13/50, 26%) gastric cancers (P<0.001). Furthermore, BACH2 promoter methylation paralleled that of previously identified targets, such as LRRC3B, LIMS2, PRKD1 and POPDC3, in a given set of gastric tumors. We propose that concerted methylation in many promoters plays a role in accelerating gastric tumor formation and that methylated promoter loci may be targets for therapeutic treatment, such as the recently introduced technique of epigenetic editing.
Keyword
BACH2Concerted methylationGastric cancerRLGS
ISSN
0304-3835
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.canlet.2014.05.009
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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