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

TitleCorrelation Between the Single-Site CpG Methylation and Expression Silencing of the XAF1 Gene in Human Gastric and Colon Cancers
Authors
Issue Date2006
PublisherWB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/gastro
Citation
Gastroenterology, 2006, v. 131 n. 6, p. 1835-1843 How to Cite?
Abstract
Background & 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.
Persistent Identifierhttp://hdl.handle.net/10722/69102
ISSN
2013 Impact Factor: 13.926
ISI Accession Number ID
References

 

Author Affiliations
  1. The University of Hong Kong
  2. Shanghai Jiaotong University
  3. Guangzhou Medical College
DC FieldValueLanguage
dc.contributor.authorZou, Ben_HK
dc.contributor.authorChim, CSen_HK
dc.contributor.authorZeng, Hen_HK
dc.contributor.authorLeung, SYen_HK
dc.contributor.authorYang, Yen_HK
dc.contributor.authorTu, SPen_HK
dc.contributor.authorLin, MCMen_HK
dc.contributor.authorWang, Jen_HK
dc.contributor.authorHe, Hen_HK
dc.contributor.authorJiang, SHen_HK
dc.contributor.authorSun, YWen_HK
dc.contributor.authorYu, LFen_HK
dc.contributor.authorYuen, STen_HK
dc.contributor.authorKung, HFen_HK
dc.contributor.authorWong, BCYen_HK
dc.date.accessioned2010-09-06T06:10:35Z-
dc.date.available2010-09-06T06:10:35Z-
dc.date.issued2006en_HK
dc.identifier.citationGastroenterology, 2006, v. 131 n. 6, p. 1835-1843en_HK
dc.identifier.issn0016-5085en_HK
dc.identifier.urihttp://hdl.handle.net/10722/69102-
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.en_HK
dc.languageengen_HK
dc.publisherWB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/gastroen_HK
dc.relation.ispartofGastroenterologyen_HK
dc.subject.meshAdulten_HK
dc.subject.meshAgeden_HK
dc.subject.meshAged, 80 and overen_HK
dc.subject.meshAntimetabolites, Antineoplastic - pharmacologyen_HK
dc.subject.meshAzacitidine - analogs & derivatives - pharmacologyen_HK
dc.subject.meshCell Line, Tumoren_HK
dc.subject.meshColonic Neoplasms - genetics - metabolismen_HK
dc.subject.meshCpG Islandsen_HK
dc.subject.meshDNA Methylationen_HK
dc.subject.meshDNA, Neoplasm - geneticsen_HK
dc.subject.meshDown-Regulation - drug effectsen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshGene Expression Regulation, Neoplastic - drug effectsen_HK
dc.subject.meshGene Silencingen_HK
dc.subject.meshHumansen_HK
dc.subject.meshHydroxamic Acids - pharmacologyen_HK
dc.subject.meshIntracellular Signaling Peptides and Proteinsen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMiddle Ageden_HK
dc.subject.meshNeoplasm Proteins - genetics - metabolismen_HK
dc.subject.meshPromoter Regions, Genetic - geneticsen_HK
dc.subject.meshProtein Synthesis Inhibitors - pharmacologyen_HK
dc.subject.meshRNA, Messenger - genetics - metabolismen_HK
dc.subject.meshStomach Neoplasms - genetics - metabolismen_HK
dc.titleCorrelation Between the Single-Site CpG Methylation and Expression Silencing of the XAF1 Gene in Human Gastric and Colon Cancersen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0016-5085&volume=131&issue=6&spage=1835&epage=1843&date=2006&atitle=Correlation+Between+the+Single-site+CpG+Methylation+and+Expression+Silencing+of+the+XAF1+Gene+in+Human+Gastric+and+Colon+Cancersen_HK
dc.identifier.emailChim, CS: jcschim@hku.hken_HK
dc.identifier.emailLeung, SY: suetyi@hku.hken_HK
dc.identifier.emailLin, MCM: mcllin@hkucc.hku.hken_HK
dc.identifier.emailWang, J: jidewang@gmail.comen_HK
dc.identifier.emailWong, BCY: bcywong@hku.hken_HK
dc.identifier.authorityChim, CS=rp00408en_HK
dc.identifier.authorityLeung, SY=rp00359en_HK
dc.identifier.authorityLin, MCM=rp00746en_HK
dc.identifier.authorityWang, J=rp00491en_HK
dc.identifier.authorityWong, BCY=rp00429en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1053/j.gastro.2006.09.050en_HK
dc.identifier.pmid17087954en_HK
dc.identifier.scopuseid_2-s2.0-33845645132en_HK
dc.identifier.hkuros125605en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33845645132&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume131en_HK
dc.identifier.issue6en_HK
dc.identifier.spage1835en_HK
dc.identifier.epage1843en_HK
dc.identifier.isiWOS:000243031100027-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridZou, B=35228257300en_HK
dc.identifier.scopusauthoridChim, CS=7004597253en_HK
dc.identifier.scopusauthoridZeng, H=7401472117en_HK
dc.identifier.scopusauthoridLeung, SY=7202044886en_HK
dc.identifier.scopusauthoridYang, Y=8675011000en_HK
dc.identifier.scopusauthoridTu, SP=7202726555en_HK
dc.identifier.scopusauthoridLin, MCM=7404816359en_HK
dc.identifier.scopusauthoridWang, J=35309087500en_HK
dc.identifier.scopusauthoridHe, H=36185495900en_HK
dc.identifier.scopusauthoridJiang, SH=7404453122en_HK
dc.identifier.scopusauthoridSun, YW=12776261000en_HK
dc.identifier.scopusauthoridYu, LF=8555658200en_HK
dc.identifier.scopusauthoridYuen, ST=7103160927en_HK
dc.identifier.scopusauthoridKung, HF=7402514190en_HK
dc.identifier.scopusauthoridWong, BCY=7402023340en_HK

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