Article: Characterization of the gene structure, functional significance, and clinical application of RNF180, a novel gene in gastric cancer

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TitleCharacterization of the gene structure, functional significance, and clinical application of RNF180, a novel gene in gastric cancer
AuthorsCheung, KF2
Lam, CNY2
Wu, K1
Ng, EKO2
Chong, WWS2
Cheng, ASL2
To, KF2
Fan, D1
Sung, JJY2
Yu, J2
Keywordsdiagnosis
epigenetic alteration
gastric cancer
prognosis
ring finger protein 180
Issue Date2012
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/28741
CitationCancer, 2012, v. 118 n. 4, p. 947-959 [How to Cite?]
DOI: http://dx.doi.org/10.1002/cncr.26189
AbstractBackground: By using genome-wide methylation screening, the authors identified ring finger protein 180 (RNF180) as preferentially methylated in cancer. This study was undertaken to clarify its structure and functional role in gastric cancer. Methods: The transcription start site and core functional promoter region of RNF180 were revealed by 5â rapid amplification of cDNA ends and luciferase activity assays. Promoter methylation was detected by combined bisulfite restriction analysis and bisulfite genomic sequencing. Cell growth was detected by colony formation assay, apoptosis by annexin V assay, and RNF180 target genes by cDNA microarray. Results: The authors revealed the transcription start site of RNF180 gene and identified the functional core promoter region (-202/+372) in the CpG island, which could be silenced by in vitro methylation assay. RNF180 was silenced in 6 of 7 gastric cancer cell lines and significantly down-regulated in primary gastric cancers compared with adjacent normal tissues (P =.001). Loss of gene expression was associated with promoter methylation. Re-expression of RNF180 suppressed cell growth (P <.001) and induced apoptosis (P <.05), which were mediated by up-regulating the antiproliferation regulators MTSS1 and CDKN2A and the proapoptotic mediator TIMP3. Promoter methylation of RNF180 was detected in 76% (150 of 198) of primary gastric cancers and 55% (11 of 20) of intestinal metaplasia, but in none of 23 normal gastric tissues. Methylated RNF180 DNA was detected in the plasma of 56% of gastric cancer patients, but not in healthy controls (P =.003). Patients with low or loss of RNF180 expression had significantly poorer overall survival. Conclusions: RNF180 is a novel potential tumor suppressor in gastric carcinogenesis and has potential clinical utility as a biomarker for gastric cancer patients. © 2011 American Cancer Society.
ISSN0008-543X
2011 Impact Factor: 4.771
2011 SCImago Journal Rankings: 0.578
DOIhttp://dx.doi.org/10.1002/cncr.26189
ISI Accession Number IDWOS:000299834300012
Funding AgencyGrant Number
Research Grants Council473008
973 national program2010CB529305
RFCID08070172
Chinese University of Hong Kong Group3110043
Chinese University of Hong Kong1903026
Funding Information:

The project was supported by a Research Grants Council grant (473008), a 973 national program fund (2010CB529305), an RFCID (08070172), a Chinese University of Hong Kong Group Research Scheme (3110043), and a Chinese University of Hong Kong Focused Investments Scheme (1903026).

ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorCheung, KF
dc.contributor.authorLam, CNY
dc.contributor.authorWu, K
dc.contributor.authorNg, EKO
dc.contributor.authorChong, WWS
dc.contributor.authorCheng, ASL
dc.contributor.authorTo, KF
dc.contributor.authorFan, D
dc.contributor.authorSung, JJY
dc.contributor.authorYu, J
dc.date.accessioned2011-08-26T14:27:53Z
dc.date.available2011-08-26T14:27:53Z
dc.date.issued2012
dc.description.abstractBackground: By using genome-wide methylation screening, the authors identified ring finger protein 180 (RNF180) as preferentially methylated in cancer. This study was undertaken to clarify its structure and functional role in gastric cancer. Methods: The transcription start site and core functional promoter region of RNF180 were revealed by 5â rapid amplification of cDNA ends and luciferase activity assays. Promoter methylation was detected by combined bisulfite restriction analysis and bisulfite genomic sequencing. Cell growth was detected by colony formation assay, apoptosis by annexin V assay, and RNF180 target genes by cDNA microarray. Results: The authors revealed the transcription start site of RNF180 gene and identified the functional core promoter region (-202/+372) in the CpG island, which could be silenced by in vitro methylation assay. RNF180 was silenced in 6 of 7 gastric cancer cell lines and significantly down-regulated in primary gastric cancers compared with adjacent normal tissues (P =.001). Loss of gene expression was associated with promoter methylation. Re-expression of RNF180 suppressed cell growth (P <.001) and induced apoptosis (P <.05), which were mediated by up-regulating the antiproliferation regulators MTSS1 and CDKN2A and the proapoptotic mediator TIMP3. Promoter methylation of RNF180 was detected in 76% (150 of 198) of primary gastric cancers and 55% (11 of 20) of intestinal metaplasia, but in none of 23 normal gastric tissues. Methylated RNF180 DNA was detected in the plasma of 56% of gastric cancer patients, but not in healthy controls (P =.003). Patients with low or loss of RNF180 expression had significantly poorer overall survival. Conclusions: RNF180 is a novel potential tumor suppressor in gastric carcinogenesis and has potential clinical utility as a biomarker for gastric cancer patients. © 2011 American Cancer Society.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationCancer, 2012, v. 118 n. 4, p. 947-959 [How to Cite?]
DOI: http://dx.doi.org/10.1002/cncr.26189
dc.identifier.doihttp://dx.doi.org/10.1002/cncr.26189
dc.identifier.eissn1097-0142
dc.identifier.epage959
dc.identifier.hkuros191077
dc.identifier.isiWOS:000299834300012
Funding AgencyGrant Number
Research Grants Council473008
973 national program2010CB529305
RFCID08070172
Chinese University of Hong Kong Group3110043
Chinese University of Hong Kong1903026
Funding Information:

The project was supported by a Research Grants Council grant (473008), a 973 national program fund (2010CB529305), an RFCID (08070172), a Chinese University of Hong Kong Group Research Scheme (3110043), and a Chinese University of Hong Kong Focused Investments Scheme (1903026).

dc.identifier.issn0008-543X
2011 Impact Factor: 4.771
2011 SCImago Journal Rankings: 0.578
dc.identifier.issue4
dc.identifier.openurl
dc.identifier.pmid21717426
dc.identifier.scopuseid_2-s2.0-84856804279
dc.identifier.spage947
dc.identifier.urihttp://hdl.handle.net/10722/137554
dc.identifier.volume118
dc.languageeng
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/28741
dc.publisher.placeUnited States
dc.relation.ispartofCancer
dc.relation.referencesReferences in Scopus
dc.rightsCancer. Copyright © John Wiley & Sons, Inc.
dc.subject.meshApoptosis - genetics - physiology
dc.subject.meshCell Line, Tumor
dc.subject.meshCell Proliferation
dc.subject.meshDNA, Neoplasm - blood - genetics
dc.subject.meshStomach Neoplasms - genetics - mortality - physiopathology
dc.subjectdiagnosis
dc.subjectepigenetic alteration
dc.subjectgastric cancer
dc.subjectprognosis
dc.subjectring finger protein 180
dc.titleCharacterization of the gene structure, functional significance, and clinical application of RNF180, a novel gene in gastric cancer
dc.typeArticle
Author Affiliations
  1. Xijing Hospital
  2. Chinese University of Hong Kong