Aberrant expression of the candidate tumor suppressor gene DAL-1 due to hypermethylation in gastric cancer

By allelotyping for loss of heterozygosity (LOH), we previously identified a deletion region that harbors the candidate tumor suppressor gene DAL-1 at 18p11.3 in sporadic gastric cancers (GCs). The expression and function of DAL-1 in GCs remained unclear. Here, we demonstrated that the absence of or...

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Main Authors:	Wang, Hao, Xu, Man, Cui, Xiaobo, Liu, Yixin, Zhang, Yi, Sui, Yu, Wang, Dong, Peng, Lei, Wang, Dexu, Yu, Jingcui
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4770418/

id	pubmed-4770418
recordtype	oai_dc
spelling	pubmed-47704182016-03-07 Aberrant expression of the candidate tumor suppressor gene DAL-1 due to hypermethylation in gastric cancer Wang, Hao Xu, Man Cui, Xiaobo Liu, Yixin Zhang, Yi Sui, Yu Wang, Dong Peng, Lei Wang, Dexu Yu, Jingcui Article By allelotyping for loss of heterozygosity (LOH), we previously identified a deletion region that harbors the candidate tumor suppressor gene DAL-1 at 18p11.3 in sporadic gastric cancers (GCs). The expression and function of DAL-1 in GCs remained unclear. Here, we demonstrated that the absence of or notable decreases in the expression of DAL-1 mRNA and protein was highly correlated with CpG hypermethylation of the DAL-1 promoter in primary GC tissues and in GC cell lines. Furthermore, abnormal DAL-1 subcellular localization was also observed in GC cells. Exogenous DAL-1 effectively inhibited cancer cell proliferation, migration, invasion and epithelial to mesenchymal transition (EMT); exogenous DAL-1 also promoted apoptosis in GC AGS cells. When endogenous DAL-1 was knocked down in GC HGC-27 cells, the cells appeared highly aggressive. Taken together, these findings provide solid evidence that aberrant expression of DAL-1 by hypermethylation in the promoter region results in tumor suppressor gene behavior that plays important roles in the malignancy of GCs. Understanding the role of it played in the molecular pathogenesis of GC, DAL-1 might be a potential biomarker for molecular diagnosis and evaluation of the GC. Nature Publishing Group 2016-02-29 /pmc/articles/PMC4770418/ /pubmed/26923709 http://dx.doi.org/10.1038/srep21755 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Wang, Hao Xu, Man Cui, Xiaobo Liu, Yixin Zhang, Yi Sui, Yu Wang, Dong Peng, Lei Wang, Dexu Yu, Jingcui
spellingShingle	Wang, Hao Xu, Man Cui, Xiaobo Liu, Yixin Zhang, Yi Sui, Yu Wang, Dong Peng, Lei Wang, Dexu Yu, Jingcui Aberrant expression of the candidate tumor suppressor gene DAL-1 due to hypermethylation in gastric cancer
author_facet	Wang, Hao Xu, Man Cui, Xiaobo Liu, Yixin Zhang, Yi Sui, Yu Wang, Dong Peng, Lei Wang, Dexu Yu, Jingcui
author_sort	Wang, Hao
title	Aberrant expression of the candidate tumor suppressor gene DAL-1 due to hypermethylation in gastric cancer
title_short	Aberrant expression of the candidate tumor suppressor gene DAL-1 due to hypermethylation in gastric cancer
title_full	Aberrant expression of the candidate tumor suppressor gene DAL-1 due to hypermethylation in gastric cancer
title_fullStr	Aberrant expression of the candidate tumor suppressor gene DAL-1 due to hypermethylation in gastric cancer
title_full_unstemmed	Aberrant expression of the candidate tumor suppressor gene DAL-1 due to hypermethylation in gastric cancer
title_sort	aberrant expression of the candidate tumor suppressor gene dal-1 due to hypermethylation in gastric cancer
description	By allelotyping for loss of heterozygosity (LOH), we previously identified a deletion region that harbors the candidate tumor suppressor gene DAL-1 at 18p11.3 in sporadic gastric cancers (GCs). The expression and function of DAL-1 in GCs remained unclear. Here, we demonstrated that the absence of or notable decreases in the expression of DAL-1 mRNA and protein was highly correlated with CpG hypermethylation of the DAL-1 promoter in primary GC tissues and in GC cell lines. Furthermore, abnormal DAL-1 subcellular localization was also observed in GC cells. Exogenous DAL-1 effectively inhibited cancer cell proliferation, migration, invasion and epithelial to mesenchymal transition (EMT); exogenous DAL-1 also promoted apoptosis in GC AGS cells. When endogenous DAL-1 was knocked down in GC HGC-27 cells, the cells appeared highly aggressive. Taken together, these findings provide solid evidence that aberrant expression of DAL-1 by hypermethylation in the promoter region results in tumor suppressor gene behavior that plays important roles in the malignancy of GCs. Understanding the role of it played in the molecular pathogenesis of GC, DAL-1 might be a potential biomarker for molecular diagnosis and evaluation of the GC.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4770418/
_version_	1613544501593243648

Aberrant expression of the candidate tumor suppressor gene DAL-1 due to hypermethylation in gastric cancer

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