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Article: Profiling of Epstein-Barr virus-encoded microRNAs in nasopharyngeal carcinoma reveals potential biomarkers and oncomirs

TitleProfiling of Epstein-Barr virus-encoded microRNAs in nasopharyngeal carcinoma reveals potential biomarkers and oncomirs
Authors
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. 3, p. 698-710 How to Cite?
AbstractBACKGROUND: Epstein-Barr virus (EBV) microRNAs are abundant in nasopharyngeal carcinoma (NPC) tumors. With recent advances in serum microRNA detection, the distinct presence of EBV microRNAs in serum could aid in screening endemic regions for NPC. A proposed network of genes targeted by these microRNAs could also shed light on EBV-associated tumorigenesis. METHODS: MicroRNA microarray profiling of 5 paired NPC biopsies was followed by validation of 12 up-regulated EBV microRNAs (BART1-3p, 2-5p, 5, 6-5p, 6-3p, 7, 8, 9, 14, 17-5p, 18-5p, 19-3p) in 15 additional cases by real-time polymerase chain reaction. Tumor (cellular) and serum microRNA copy numbers from the same 15 patients were correlated. Expression of the same microRNAs were also examined in EBV-positive cell lines C666 and NP460hTERT+EBV. Bioinformatic tools helped predict cellular target genes, which were later confirmed by gene expression analysis. RESULTS: The authors' high-throughput approach shows that EBV microRNAs are generally more up-regulated than microRNAs of human origin. Twenty-nine of 39 EBV microRNAs were significantly up-regulated in tumor versus their nontumor biopsies (P <.05). Upon successfully validating 12 selected EBV microRNAs in 15 additional paired NPC cases, the authors found that their distinct presence in the serum of NPC patients positively correlated with cellular copy numbers of EBV microRNAs. Further investigation of potential EBV microRNA target genes revealed inhibition of tumor suppressor genes (eg, PTEN) and extensive deregulation of several pathways frequently involved in NPC (eg, Wnt signaling). CONCLUSIONS: Increasing knowledge of host-virus interaction via microRNAs may provide feasible explanations underlying NPC tumorigenesis along with the development of biomarkers for screening high-risk populations. © 2011 American Cancer Society.
Persistent Identifierhttp://hdl.handle.net/10722/139119
ISSN
2015 Impact Factor: 5.649
2015 SCImago Journal Rankings: 3.188
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong UGCAoE/M-06/08
Sun Yat-Sen University85
000-3171311
Funding Information:

This work was supported by a Hong Kong UGC Area of Excellent Scheme (AoE/M-06/08) and the Hundred Talents Program at Sun Yat-Sen University (85,000-3171311). Immortalized nasopharynx epithelial cell lines NP460hTERT+EBV and NP69 have been kindly provided by Professor George S. W. Tsao from the Department of Anatomy, University of Hong Kong.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorWong, AMGen_HK
dc.contributor.authorKong, KLen_HK
dc.contributor.authorTsang, JWHen_HK
dc.contributor.authorKwong, DLWen_HK
dc.contributor.authorGuan, XYen_HK
dc.date.accessioned2011-09-23T05:45:13Z-
dc.date.available2011-09-23T05:45:13Z-
dc.date.issued2012en_HK
dc.identifier.citationCancer, 2012, v. 118 n. 3, p. 698-710en_HK
dc.identifier.issn0008-543Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/139119-
dc.description.abstractBACKGROUND: Epstein-Barr virus (EBV) microRNAs are abundant in nasopharyngeal carcinoma (NPC) tumors. With recent advances in serum microRNA detection, the distinct presence of EBV microRNAs in serum could aid in screening endemic regions for NPC. A proposed network of genes targeted by these microRNAs could also shed light on EBV-associated tumorigenesis. METHODS: MicroRNA microarray profiling of 5 paired NPC biopsies was followed by validation of 12 up-regulated EBV microRNAs (BART1-3p, 2-5p, 5, 6-5p, 6-3p, 7, 8, 9, 14, 17-5p, 18-5p, 19-3p) in 15 additional cases by real-time polymerase chain reaction. Tumor (cellular) and serum microRNA copy numbers from the same 15 patients were correlated. Expression of the same microRNAs were also examined in EBV-positive cell lines C666 and NP460hTERT+EBV. Bioinformatic tools helped predict cellular target genes, which were later confirmed by gene expression analysis. RESULTS: The authors' high-throughput approach shows that EBV microRNAs are generally more up-regulated than microRNAs of human origin. Twenty-nine of 39 EBV microRNAs were significantly up-regulated in tumor versus their nontumor biopsies (P <.05). Upon successfully validating 12 selected EBV microRNAs in 15 additional paired NPC cases, the authors found that their distinct presence in the serum of NPC patients positively correlated with cellular copy numbers of EBV microRNAs. Further investigation of potential EBV microRNA target genes revealed inhibition of tumor suppressor genes (eg, PTEN) and extensive deregulation of several pathways frequently involved in NPC (eg, Wnt signaling). CONCLUSIONS: Increasing knowledge of host-virus interaction via microRNAs may provide feasible explanations underlying NPC tumorigenesis along with the development of biomarkers for screening high-risk populations. © 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.subject.meshAdulten_HK
dc.subject.meshAgeden_HK
dc.subject.meshBlotting, Westernen_HK
dc.subject.meshCase-Control Studiesen_HK
dc.subject.meshEpstein-Barr Virus Infections - blood - genetics - virologyen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshGene Expression Profilingen_HK
dc.subject.meshHerpesvirus 4, Human - genetics - isolation & purificationen_HK
dc.subject.meshHumansen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMicroRNAs - blood - geneticsen_HK
dc.subject.meshMiddle Ageden_HK
dc.subject.meshNasopharyngeal Neoplasms - blood - genetics - virologyen_HK
dc.subject.meshOligonucleotide Array Sequence Analysisen_HK
dc.subject.meshOncogenesen_HK
dc.subject.meshPrognosisen_HK
dc.subject.meshRNA, Viral - blood - geneticsen_HK
dc.subject.meshReal-Time Polymerase Chain Reactionen_HK
dc.subject.meshTumor Markers, Biological - geneticsen_HK
dc.titleProfiling of Epstein-Barr virus-encoded microRNAs in nasopharyngeal carcinoma reveals potential biomarkers and oncomirsen_HK
dc.typeArticleen_HK
dc.identifier.emailTsang, JWH:jwhtsang@hku.hken_HK
dc.identifier.emailKwong, DLW:dlwkwong@hku.hken_HK
dc.identifier.emailGuan, XY:xyguan@hkucc.hku.hken_HK
dc.identifier.authorityTsang, JWH=rp00278en_HK
dc.identifier.authorityKwong, DLW=rp00414en_HK
dc.identifier.authorityGuan, XY=rp00454en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1002/cncr.26309en_HK
dc.identifier.pmid21720996-
dc.identifier.scopuseid_2-s2.0-84856211556en_HK
dc.identifier.hkuros194833en_US
dc.identifier.hkuros203477-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84856211556&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume118en_HK
dc.identifier.issue3en_HK
dc.identifier.spage698en_HK
dc.identifier.epage710en_HK
dc.identifier.eissn1097-0142-
dc.identifier.isiWOS:000299335500015-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectCentre for Nasopharyngeal Carcinoma Research-
dc.identifier.scopusauthoridWong, AMG=37462381500en_HK
dc.identifier.scopusauthoridKong, KL=36106004300en_HK
dc.identifier.scopusauthoridTsang, JWH=35141929400en_HK
dc.identifier.scopusauthoridKwong, DLW=15744231600en_HK
dc.identifier.scopusauthoridGuan, XY=7201463221en_HK

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