Article: Correlation Between the Single-Site CpG Methylation and Expression Silencing of the XAF1 Gene in Human Gastric and Colon Cancers

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TitleCorrelation Between the Single-Site CpG Methylation and Expression Silencing of the XAF1 Gene in Human Gastric and Colon Cancers
AuthorsZou, B2 3
Chim, CS1
Zeng, H3
Leung, SY1
Yang, Y1
Tu, SP1
Lin, MCM1
Wang, J1
He, H1
Jiang, SH2
Sun, YW1 2
Yu, LF1 2
Yuen, ST1
Kung, HF1
Wong, BCY1
Issue Date2006
PublisherWB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/gastro
CitationGastroenterology, 2006, v. 131 n. 6, p. 1835-1843 [How to Cite?]
DOI: http://dx.doi.org/10.1053/j.gastro.2006.09.050
AbstractBackground & Aims: X-linked inhibitor of apoptosis protein (XIAP)-associated factor 1 (XAF1) antagonizes the anti-caspase activity of XIAP. XAF1 messenger RNA is present in normal tissues but undetectable in various cancers and thus poses a potential tumor suppressor gene. The aim of this study was to examine the novel pattern of methylation of XAF1 in gastric and colon cancers and locate the important CpG sites for transcriptional regulation and tumor progression. Methods: XAF1 expression was detected by reverse-transcription polymerase chain reaction (PCR) and Western blot analysis. Four different fragments around the transcription start site of XAF1 were cloned and examined putative promoter activities by luciferase reporter assay. Each CpG site in fragment F291 was mutated by site-directed mutagenesis technique, and the change of promoter activity of this fragment was detected by luciferase reporter assay. Methylation status of XAF1 was determined by methylation-specific PCR (MSP) and bisulfite DNA sequencing PCR analysis. Results: Down-regulation of XAF1 in association with hypermethylation was detected in 3 of 4 human gastric cancer cell lines and 6 of 8 colon cancer cell lines. Of the 4 promoter fragments, F291 showed the highest promoter activity, which could be down-regulated obviously by the mutation of particular CpG sites. Moreover, aberrant hypermethylation of these important CpG sites was strongly associated with the development of gastric and colon cancers. Conclusions: A cluster of methylated CpG sites instead of CpG islands located in the promoter area resulted in gene silencing of XAF1, and CpGs at -2nd, -1st, and +3rd positions are functionally more important in its transcriptional regulation. © 2006 AGA Institute.
ISSN0016-5085
2011 Impact Factor: 11.675
2011 SCImago Journal Rankings: 1.055
DOIhttp://dx.doi.org/10.1053/j.gastro.2006.09.050
ISI Accession Number IDWOS:000243031100027
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorZou, B
dc.contributor.authorChim, CS
dc.contributor.authorZeng, H
dc.contributor.authorLeung, SY
dc.contributor.authorYang, Y
dc.contributor.authorTu, SP
dc.contributor.authorLin, MCM
dc.contributor.authorWang, J
dc.contributor.authorHe, H
dc.contributor.authorJiang, SH
dc.contributor.authorSun, YW
dc.contributor.authorYu, LF
dc.contributor.authorYuen, ST
dc.contributor.authorKung, HF
dc.contributor.authorWong, BCY
dc.date.accessioned2010-09-06T06:10:35Z
dc.date.available2010-09-06T06:10:35Z
dc.date.issued2006
dc.description.abstractBackground & Aims: X-linked inhibitor of apoptosis protein (XIAP)-associated factor 1 (XAF1) antagonizes the anti-caspase activity of XIAP. XAF1 messenger RNA is present in normal tissues but undetectable in various cancers and thus poses a potential tumor suppressor gene. The aim of this study was to examine the novel pattern of methylation of XAF1 in gastric and colon cancers and locate the important CpG sites for transcriptional regulation and tumor progression. Methods: XAF1 expression was detected by reverse-transcription polymerase chain reaction (PCR) and Western blot analysis. Four different fragments around the transcription start site of XAF1 were cloned and examined putative promoter activities by luciferase reporter assay. Each CpG site in fragment F291 was mutated by site-directed mutagenesis technique, and the change of promoter activity of this fragment was detected by luciferase reporter assay. Methylation status of XAF1 was determined by methylation-specific PCR (MSP) and bisulfite DNA sequencing PCR analysis. Results: Down-regulation of XAF1 in association with hypermethylation was detected in 3 of 4 human gastric cancer cell lines and 6 of 8 colon cancer cell lines. Of the 4 promoter fragments, F291 showed the highest promoter activity, which could be down-regulated obviously by the mutation of particular CpG sites. Moreover, aberrant hypermethylation of these important CpG sites was strongly associated with the development of gastric and colon cancers. Conclusions: A cluster of methylated CpG sites instead of CpG islands located in the promoter area resulted in gene silencing of XAF1, and CpGs at -2nd, -1st, and +3rd positions are functionally more important in its transcriptional regulation. © 2006 AGA Institute.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationGastroenterology, 2006, v. 131 n. 6, p. 1835-1843 [How to Cite?]
DOI: http://dx.doi.org/10.1053/j.gastro.2006.09.050
dc.identifier.doihttp://dx.doi.org/10.1053/j.gastro.2006.09.050
dc.identifier.epage1843
dc.identifier.hkuros125605
dc.identifier.isiWOS:000243031100027
dc.identifier.issn0016-5085
2011 Impact Factor: 11.675
2011 SCImago Journal Rankings: 1.055
dc.identifier.issue6
dc.identifier.openurl
dc.identifier.pmid17087954
dc.identifier.scopuseid_2-s2.0-33845645132
dc.identifier.spage1835
dc.identifier.urihttp://hdl.handle.net/10722/69102
dc.identifier.volume131
dc.languageeng
dc.publisherWB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/gastro
dc.publisher.placeUnited States
dc.relation.ispartofGastroenterology
dc.relation.referencesReferences in Scopus
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshAged, 80 and over
dc.subject.meshAntimetabolites, Antineoplastic - pharmacology
dc.subject.meshAzacitidine - analogs & derivatives - pharmacology
dc.subject.meshCell Line, Tumor
dc.subject.meshColonic Neoplasms - genetics - metabolism
dc.subject.meshCpG Islands
dc.subject.meshDNA Methylation
dc.subject.meshDNA, Neoplasm - genetics
dc.subject.meshDown-Regulation - drug effects
dc.subject.meshFemale
dc.subject.meshGene Expression Regulation, Neoplastic - drug effects
dc.subject.meshGene Silencing
dc.subject.meshHumans
dc.subject.meshHydroxamic Acids - pharmacology
dc.subject.meshIntracellular Signaling Peptides and Proteins
dc.subject.meshMale
dc.subject.meshMiddle Aged
dc.subject.meshNeoplasm Proteins - genetics - metabolism
dc.subject.meshPromoter Regions, Genetic - genetics
dc.subject.meshProtein Synthesis Inhibitors - pharmacology
dc.subject.meshRNA, Messenger - genetics - metabolism
dc.subject.meshStomach Neoplasms - genetics - metabolism
dc.titleCorrelation Between the Single-Site CpG Methylation and Expression Silencing of the XAF1 Gene in Human Gastric and Colon Cancers
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong
  2. Shanghai Jiaotong University
  3. Guangzhou Medical College