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

Author

Listed:
  • Longmei Cai

    (Cancer Research Institute, Southern Medical University)

  • Yanfen Ye

    (Cancer Research Institute, Southern Medical University
    The First Affiliated Hospital, Wannan Medical College)

  • 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
    Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital)

  • Xin Li

    (Cancer Research Institute, Southern Medical University)

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.

Suggested Citation

  • Longmei Cai & Yanfen Ye & Qiang Jiang & Yuxiang Chen & Xiaoming Lyu & Jinbang Li & Shuang Wang & Tengfei Liu & Hongbing Cai & Kaitai Yao & Ji-Liang Li & Xin Li, 2015. "Epstein–Barr virus-encoded microRNA BART1 induces tumour metastasis by regulating PTEN-dependent pathways in nasopharyngeal carcinoma," Nature Communications, Nature, vol. 6(1), pages 1-13, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8353
    DOI: 10.1038/ncomms8353
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