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.
DOI
10.1038/ncomms8353
Publication Date
2015-07-02
Publication Title
Nature Communications
Volume
6
Issue
1
Publisher
Springer Science and Business Media LLC
ISSN
2041-1723
Embargo Period
2024-11-19
Recommended Citation
Cai, L., Ye, Y., Jiang, Q., Chen, Y., & et al. (2015) 'Epstein–Barr virus-encoded microRNA BART1 induces tumour metastasis by regulating PTEN-dependent pathways in nasopharyngeal carcinoma', Nature Communications, 6(1). Springer Science and Business Media LLC: Available at: https://doi.org/10.1038/ncomms8353
