Journal
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
Volume 37, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s13046-018-0953-6
Keywords
Nasopharyngeal carcinoma; Epithelial-mesenchymal transition; Metastasis; Epstein-Barr virus; EBV-miR-BART8-3p; NF-B signaling; Erk1; 2 signaling
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Funding
- National Natural Science Foundation of China [U1405221, 81470134, 81341108]
- Science and Technology Project of Fujian Province [2015Y0051, 2018 J01275]
- Medical Innovation Project of Fujian Province [2015-CX-6]
- Fujian Provincial Health and Family Planning Commission [2012-1-6]
- Research Grants Council of the Hong Kong SAR [17154516, C7027-16G]
- Health and Medical Research Fund [14131032]
- Areas of Excellence Scheme of the University Grants Committee [AoE/M-06/08]
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BackgroundEpstein-Barr virus (EBV) is ubiquitously associated with nasopharyngeal carcinoma (NPC). EBV encodes two groups of microRNAs (miRNAs) which are divided into BamHI fragment H rightward open reading frame 1 (BHRF1) and BamHI-A rightward transcripts (BART) microRNAs. EBV miR-BART has been found to be involved in the development and progression of NPC. However, so far the role of EBV-miR-BART8-3p in NPC progression remains unknown. This study aimed to investigate the role of EBV-miR-BART8-3p in NPC and explore the underlying mechanisms.MethodsmiRNA expression was profiled in NPC and normal nasopharyngeal mucosal specimens using miRNA sequencing. EBV-miR-BART8-3p and RNF38 expression was quantified with qPCR assay. The migration, invasion and metastasis of NPC cells were evaluated using CCK-8, colony-forming, wound-healing, and migration and invasion assays. The expression levels of epithelial-mesenchymal transition (EMT)-related markers,metastasis-related markers and NF-B and Erk1/2 signaling proteins were determined using Western blotting. Tumorigenic assay was performed to evaluate the pulmonary metastatic ability of NPC cells in vivo.ResultsEBV BART miRNAs were highly over-expressed and co-expressed in NPC and might be associated with deactivated immune response in NPC according to the sequencing analysis. EBV-miR-BART8-3p expression was significantly higher in human NPC specimens than in normal nasopharyngeal mucosal specimens. EBV-miR-BART8-3p was found to promote NPC migration, invasion and metastasis, drove an EMT process and upregulated expression of metastasis-related proteins expression in NPC cells. Our data showed EBV-miR-BART8-3p directly targeted RNF38 in NPC cells.ConclusionThe present study demonstrates that EBV-miR-BART8-3p plays a significant role in inducing EMT and promoting metastasis through directly targeting RNF38 in NPC cells via the activation of NF-B and Erk1/2 signaling pathways. Our findings suggest that EBV-miR-BART8-3p is a potential therapeutic target for NPC.
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