EBV-miR-BART8-3p induces epithelial-mesenchymal transition and promotes metastasis of nasopharyngeal carcinoma cells through activating NF-κB and Erk1/2 pathways

• Published in: Journal of experimental & clinical cancer research Vol. 37; no. 1; pp. 283 - 14
• Main Authors: Lin, Cheng, Zong, Jingfeng, Lin, Wansong, Wang, Minghui, Xu, Yuanji, Zhou, Rui, Lin, Shaojun, Guo, Qiaojuan, Chen, Honglin, Ye, Yunbin, Zhang, Bin, Pan, Jianji
• Format: Journal Article
• Language: English
• Published: England BioMed Central 26.11.2018; BMC
• Subjects: Cloning; EBV-miR-BART8-3p; Epigenetics; Epithelial-mesenchymal transition; Epstein-Barr virus; Genomes; Kinases; Laboratory animals; Lung cancer; Medical prognosis; Metastasis; MicroRNAs; Mutation; Nasopharyngeal carcinoma; NF-κB signaling; Proteins; Throat cancer; United States > US; China; NF-κB signaling; Nasopharyngeal carcinoma; Epithelial-mesenchymal transition; EBV-miR-BART8-3p; Epstein-Barr virus; Metastasis; Erk1/2 signaling
• ISSN: 1756-9966; 0392-9078; 1756-9966
• DOI: 10.1186/s13046-018-0953-6

Epstein-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. miRNA 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-κB 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. EBV 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. The 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-κB and Erk1/2 signaling pathways. Our findings suggest that EBV-miR-BART8-3p is a potential therapeutic target for NPC.