Epstein–Barr virus-encoded microRNA BART1 induces tumour metastasis by regulating PTEN-dependent pathways in nasopharyngeal carcinoma

Longmei Cai, Yanfen Ye, Qiang Jiang, Yuxiang Chen, Xiaoming Lyu, Jinbang Li, Shuang Wang, Tengfei Liu, Hongbing Cai, Kaitai Yao, Ji-Liang Li () and Xin Li ()
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Longmei Cai: Cancer Research Institute, Southern Medical University
Yanfen Ye: Cancer Research Institute, Southern Medical University
Qiang Jiang: Cancer Research Institute, Southern Medical University
Yuxiang Chen: Cancer Research Institute, Southern Medical University
Xiaoming Lyu: Cancer Research Institute, Southern Medical University
Jinbang Li: Cancer Research Institute, Southern Medical University
Shuang Wang: Basic Medical College, Southern Medical University
Tengfei Liu: Basic Medical College, Southern Medical University
Hongbing Cai: School of Traditional Chinese Medicine, Southern Medical University
Kaitai Yao: Cancer Research Institute, Southern Medical University
Ji-Liang Li: School of Biotechnology, Southern Medical University
Xin Li: Cancer Research Institute, Southern Medical University

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: 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-p130Cas 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.

Date: 2015
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DOI: 10.1038/ncomms8353

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