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

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

• Authors: Cheng Lin, Jingfeng Zong, Wansong Lin, Minghui Wang, Yuanji Xu, Rui Zhou, Shaojun Lin, Qiaojuan Guo, Honglin Chen, Yunbin Ye, Bin Zhang, Jianji Pan
• Journal: Journal of experimental & clinical cancer research : CR (J Exp Clin Cancer Res) Vol. 37 Issue 1 Pg. 283 (Nov 26 2018) ISSN: 1756-9966 [Electronic] England
• PMID: 30477559 (Publication Type: Journal Article)

Chemical References

• MicroRNAs
• NF-kappa B

Topics

• Animals
• Cell Line, Tumor
• Cell Proliferation
• Epithelial-Mesenchymal Transition
• Epstein-Barr Virus Infections (genetics, metabolism, pathology, virology)
• Female
• Herpesvirus 4, Human (genetics, metabolism)
• Humans
• MAP Kinase Signaling System
• Mice
• Mice, Nude
• MicroRNAs (genetics, metabolism)
• NF-kappa B (metabolism)
• Nasopharyngeal Carcinoma (genetics, metabolism, pathology, virology)
• Neoplasm Metastasis
• Transfection