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

TitleCharacterization of the gene structure, functional significance, and clinical application of RNF180, a novel gene in gastric cancer
Authors
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
Citation
Cancer, 2012, v. 118 n. 4, p. 947-959 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/137554
ISSN
2014 Impact Factor: 4.889
2014 SCImago Journal Rankings: 2.510
ISI Accession Number ID
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).

References

 

DC FieldValueLanguage
dc.contributor.authorCheung, KFen_HK
dc.contributor.authorLam, CNYen_HK
dc.contributor.authorWu, Ken_HK
dc.contributor.authorNg, EKOen_HK
dc.contributor.authorChong, WWSen_HK
dc.contributor.authorCheng, ASLen_HK
dc.contributor.authorTo, KFen_HK
dc.contributor.authorFan, Den_HK
dc.contributor.authorSung, JJYen_HK
dc.contributor.authorYu, Jen_HK
dc.date.accessioned2011-08-26T14:27:53Z-
dc.date.available2011-08-26T14:27:53Z-
dc.date.issued2012en_HK
dc.identifier.citationCancer, 2012, v. 118 n. 4, p. 947-959en_HK
dc.identifier.issn0008-543Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/137554-
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.en_HK
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/28741en_HK
dc.relation.ispartofCanceren_HK
dc.rightsCancer. Copyright © John Wiley & Sons, Inc.-
dc.subjectdiagnosisen_HK
dc.subjectepigenetic alterationen_HK
dc.subjectgastric canceren_HK
dc.subjectprognosisen_HK
dc.subjectring finger protein 180en_HK
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.titleCharacterization of the gene structure, functional significance, and clinical application of RNF180, a novel gene in gastric canceren_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1097-0142 (Electronic) 0008-543X (Linkin&volume=&spage=&epage=&date=2011&atitle=Characterization+of+the+gene+structure,+functional+significance,+and+clinical+application+of+RNF180,+a+novel+gene+in+gastric+canceren_US
dc.identifier.emailNg, EKO: ngko@hku.hken_HK
dc.identifier.authorityNg, EKO=rp01364en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/cncr.26189en_HK
dc.identifier.pmid21717426en_HK
dc.identifier.scopuseid_2-s2.0-84856804279en_HK
dc.identifier.hkuros191077en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84856804279&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume118en_HK
dc.identifier.issue4en_HK
dc.identifier.spage947en_HK
dc.identifier.epage959en_HK
dc.identifier.eissn1097-0142-
dc.identifier.isiWOS:000299834300012-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridCheung, KF=7402406701en_HK
dc.identifier.scopusauthoridLam, CNY=8940435600en_HK
dc.identifier.scopusauthoridWu, K=8947728400en_HK
dc.identifier.scopusauthoridNg, EKO=21135553700en_HK
dc.identifier.scopusauthoridChong, WWS=24576241300en_HK
dc.identifier.scopusauthoridCheng, ASL=7402075036en_HK
dc.identifier.scopusauthoridTo, KF=7101911940en_HK
dc.identifier.scopusauthoridFan, D=7202965595en_HK
dc.identifier.scopusauthoridSung, JJY=35405352400en_HK
dc.identifier.scopusauthoridYu, J=35351306800en_HK

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