Epstein–Barr virus-encoded microRNA BART1 induces tumour metastasis by regulating PTEN-dependent pathways in nasopharyngeal carcinoma
Open Access
- 2 July 2015
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 6 (1), 7353
- https://doi.org/10.1038/ncomms8353
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.This publication has 67 references indexed in Scilit:
- EBV and human microRNAs co-target oncogenic and apoptotic viral and human genes during latencyThe EMBO Journal, 2012
- Endogenous viruses: insights into viral evolution and impact on host biologyNature Reviews Genetics, 2012
- Viral MicroRNA Targetome of KSHV-Infected Primary Effusion Lymphoma Cell LinesCell Host & Microbe, 2011
- The microRNAs of Epstein–Barr Virus are expressed at dramatically differing levels among cell linesVirology, 2009
- MicroRNA deregulation and pathway alterations in nasopharyngeal carcinomaBritish Journal of Cancer, 2009
- Tenets of PTEN Tumor SuppressionCell, 2008
- Downregulated NM23-H1 expression is associated with intracranial invasion of nasopharyngeal carcinomaBritish Journal of Cancer, 2008
- Modulation of LMP1 protein expression by EBV-encoded microRNAsProceedings of the National Academy of Sciences of the United States of America, 2007
- Oncomirs — microRNAs with a role in cancerNature Reviews Cancer, 2006
- Complex networks orchestrate epithelial–mesenchymal transitionsNature Reviews Molecular Cell Biology, 2006