Modulation of LMP1 protein expression by EBV-encoded microRNAs

Angela Kwok Fung Lo, Fai To Ka, Wai Lo Kwok, Raymond Wai Ming Lung, Jan Wai Ying Hui, Gangling Liao, S. Diane Hayward

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)16164-16169
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number41
DOIs
StatePublished - Oct 9 2007

Keywords

  • Epstein-Barr virus
  • Nasopharyngeal carcinoma

ASJC Scopus subject areas

  • General

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