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dc.contributor.authorCai, Len
dc.contributor.authorYe, Yen
dc.contributor.authorJiang, Qen
dc.contributor.authorChen, Yen
dc.contributor.authorLyu, Xen
dc.contributor.authorLi, Jen
dc.contributor.authorWang, Sen
dc.contributor.authorLiu, Ten
dc.contributor.authorCai, Hen
dc.contributor.authorYao, Ken
dc.contributor.authorLi, J-Len
dc.contributor.authorLi, Xen
dc.date.accessioned2016-08-09T14:48:42Z
dc.date.available2016-08-09T14:48:42Z
dc.date.issued2015-07-02en
dc.identifier.urihttp://hdl.handle.net/10026.1/5246
dc.description.abstract

Epstein-Barr virus (EBV), aetiologically linked to nasopharyngeal carcinoma (NPC), is the first human virus found to encode many miRNAs. However, how these viral miRNAs precisely regulate the tumour metastasis in NPC remains obscure. Here we report that EBV-miR-BART1 is highly expressed in NPC and closely associated with pathological and advanced clinical stages of NPC. Alteration of EBV-miR-BART1 expression results in an increase in migration and invasion of NPC cells in vitro and causes tumour metastasis in vivo. Mechanistically, EBV-miR-BART1 directly targets the cellular tumour suppressor PTEN. Reduction of PTEN dosage by EBV-miR-BART1 activates PTEN-dependent pathways including PI3K-Akt, FAK-p130(Cas) and Shc-MAPK/ERK1/2 signalling, drives EMT, and consequently increases migration, invasion and metastasis of NPC cells. Reconstitution of PTEN rescues all phenotypes generated by EBV-miR-BART1, highlighting the role of PTEN in EBV-miR-BART-driven metastasis in NPC. Our findings provide new insights into the metastasis of NPC regulated by EBV and advocate for developing clinical intervention strategies against NPC.

en
dc.format.extent7353 - ?en
dc.languageengen
dc.language.isoengen
dc.subjectAdulten
dc.subjectAnimalsen
dc.subjectBlotting, Westernen
dc.subjectCarcinomaen
dc.subjectCarcinoma, Squamous Cellen
dc.subjectCell Line, Tumoren
dc.subjectFemaleen
dc.subjectGene Expression Regulation, Neoplasticen
dc.subjectHEK293 Cellsen
dc.subjectHead and Neck Neoplasmsen
dc.subjectHerpesvirus 4, Humanen
dc.subjectHumansen
dc.subjectImmunohistochemistryen
dc.subjectMaleen
dc.subjectMiceen
dc.subjectMice, Nudeen
dc.subjectMicroRNAsen
dc.subjectNasopharyngeal Carcinomaen
dc.subjectNasopharyngeal Neoplasmsen
dc.subjectNeoplasm Metastasisen
dc.subjectNeoplasm Transplantationen
dc.subjectPTEN Phosphohydrolaseen
dc.subjectRNA, Viralen
dc.subjectReal-Time Polymerase Chain Reactionen
dc.subjectSignal Transductionen
dc.subjectSquamous Cell Carcinoma of Head and Necken
dc.titleEpstein-Barr virus-encoded microRNA BART1 induces tumour metastasis by regulating PTEN-dependent pathways in nasopharyngeal carcinoma.en
dc.typeJournal Article
plymouth.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/26135619en
plymouth.volume6en
plymouth.publication-statusPublished onlineen
plymouth.journalNat Communen
dc.identifier.doi10.1038/ncomms8353en
plymouth.organisational-group/Plymouth
plymouth.organisational-group/Plymouth/00 Groups by role
plymouth.organisational-group/Plymouth/00 Groups by role/Academics
plymouth.organisational-group/Plymouth/Faculty of Medicine and Dentistry
plymouth.organisational-group/Plymouth/Faculty of Medicine and Dentistry/Biomedical Research Group
plymouth.organisational-group/Plymouth/Faculty of Medicine and Dentistry/Biomedical Research Group/RC Reporting Group BRG
plymouth.organisational-group/Plymouth/Faculty of Medicine and Dentistry/Collaboration for the Advancement of Medical Education Research Assessment
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine
dc.publisher.placeEnglanden
dcterms.dateAccepted2015-04-29en
dc.identifier.eissn2041-1723en
dc.rights.embargoperiodNot knownen
rioxxterms.versionofrecord10.1038/ncomms8353en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2015-07-02en
rioxxterms.typeJournal Article/Reviewen


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