title: Epstein-Barr virus-encoded microRNA BART1 induces tumour metastasis by regulating PTEN-dependent pathways in nasopharyngeal carcinoma.
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.
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Longmei
authors.initials: L
authors.lastname: Cai
authors.affiliation: 1] Cancer Research Institute, Southern Medical University, Guangzhou 510515, China [2] Radiation Department, The First Affiliated Hospital, Wannan Medical College, Wuhu 241001, China.
authors.forename: Yanfen
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Lyu
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Jinbang
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pathology, Basic Medical College, Southern Medical University, Guangzhou 510515, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pathology, Basic Medical College, Southern Medical University, Guangzhou 510515, China.
authors.forename: Tengfei
authors.initials: T
authors.lastname: Liu
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Cai
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Kaitai
authors.initials: K
authors.lastname: Yao
authors.affiliation: 1] School of Biotechnology, Southern Medical University, Guangzhou 510515, China [2] Molecular Oncology Laboratories, Department of Oncology, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK.
authors.forename: Ji-Liang
authors.initials: JL
authors.lastname: Li
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
mesh_terms: D000328:Adult; D000818:Animals; D015153:Blotting, Western; D002277:Carcinoma; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006258:Head and Neck Neoplasms / Q000235:genetics*; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000235:genetics; D009368:Neoplasm Transplantation; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: C000606396:MIRN-BART1 microRNA, human; D035683:MicroRNAs; D012367:RNA, Viral; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human