Modulation of LMP1 protein expression by EBV-encoded microRNAs

  • Angela Kwok Fung Lo
    *Viral Oncology Program, Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD 21231;
  • Ka Fai To
    Department of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China,
  • Kwok Wai Lo
    Department of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China,
  • Raymond Wai Ming Lung
    Department of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China,
  • Jan Wai Ying Hui
    Department of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China,
  • Gangling Liao
    *Viral Oncology Program, Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD 21231;
  • S. Diane Hayward
    *Viral Oncology Program, Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD 21231;

書誌事項

公開日
2007-10-09
DOI
  • 10.1073/pnas.0702896104
公開者
Proceedings of the National Academy of Sciences

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説明

<jats:p>Epstein–Barr virus (EBV) was the first human virus found to encode microRNAs (miRNAs), but the function of these miRNAs has been obscure. Nasopharyngeal carcinoma (NPC) is associated with EBV infection, and the EBV-encoded LMP1 is believed to be a key factor in NPC development. However, detection of LMP1 protein in NPC is variable. Here, we report that EBV-encoded BART miRNAs target the 3′ UTR of the LMP1 gene and negatively regulate LMP1 protein expression. These miRNAs also modulate LMP1-induced NF-κB signaling and alleviate the cisplatin sensitivity of LMP1-expressing NPC cells. Consistent with a previous study on the NPC C666-1 cell line and C15 xenograft, we found abundant expression of BART miRNAs in NPC tissues. Furthermore, DNA sequencing revealed that the 3′ UTR of LMP1 is highly conserved in NPC-derived EBV isolates. The data provide insight into the discrepancy between LMP1 transcript and protein detection in NPC and highlight the role of the EBV miRNAs in regulating LMP1 downstream signaling to promote cancer development.</jats:p>

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