The Study of EBV Encoded BART9 microRNA and Its Roles in Nasopharyngeal Carcinoma Metastasis

  • Chen, Hua-Chien (PI)

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details


Background: Nasopharyngeal carcinoma (NPC) is a human malignancy in which cancer cells arise from the epithelial cells of the nasopharynx tissue. In advanced stages, NPC is a highly metastatic cancer. The mechanisms underlying the highly metastatic nature of NPC remain unclear. Compelling evidence indicate that EBV is a causal agent of NPC and suggest that products of EBV genome are involved in the development of the malignancy. In addition to viral proteins, EBV also encodes several microRNAs. Recently, utilizing the next generation sequencing technology, we discovered that the EBV-encoded microRNA BART9 was expressed at high levels in NPC tissues. The abundance of BART9 was higher than the best documented human oncogenic microRNA, miR-21. Computational analysis revealed that several migration-related pathways are enriched with putative targets of BART9, including E-cadherin, a critical regulator in epithelial-mesenchymal transition (EMT) and cell migration and invasion. Over-expression of BART9 decreased the mRNA and protein levels of E-cadherin and induced a translocation of beta-catenin in NPC cells. BART9-expressing cells displayed a fibroblast-like morphology with enhanced the migration and invasion capability. In contrast, depleting endogenous BART9 reduced the migratory capability of EBV-positive NPC cells. Interestingly, the seed sequence of BART9 was highly similar to the seed sequence of human miR-200 family miRNAs, a miRNA family frequently down-regulated in tumors, including NPC. miR-200 family miRNAs have been shown to play a critical role in regulation of EMT and cell migration. Over-expression of BART9 down-regulates the levels of miR-200 family miRNAs in NPC. These data suggest that BART9 may promote cell migration and invasion by simultaneously regulating human protein-coding genes and miRNAs in NPC. Aim and strategy: In this proposal, we aim to elucidate the role of BART9 in NPC tumorigenesis. Three specific aims are proposed. Firstly, we will use in vivo animal models to investigate the effect of BART9 in the metastasis of NPC. Secondly, we will characterize the cellular events and the molecular targets and pathways associated with BART9-mediated migration, invasion and tumor metastasis. Finally, we will investigate the potential interaction between BART9 and human miR-200 family miRNAs. Significance and future application: The ultimate goal of this study is to explore the potential of targeting EBV-encoded microRNAs for NPC diagnosis, prognosis and therapeutics. The proposed studies could advance our understanding of the biological functions and pathways regulated by BART9 and provide useful strategies to control the progression of NPC. In addition, the knowledge gained from this study will help to understand the interaction between virus- and host-encoded microRNAs. This information can potentially be extended to other virus-encoded microRNAs and can be used in both basic and translational research.

Project IDs

Project ID:PC10301-0916
External Project ID:NSC101-2320-B182-013-MY3
Effective start/end date01/08/1431/07/15


  • EBV virus
  • microRNA
  • Cell migration
  • Tumor metastasis
  • Nasopharyngeal carcinoma (NPC)


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