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J Exp Clin Cancer Res. 2018 Nov 26;37(1):283. doi: 10.1186/s13046-018-0953-6.

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

Author information

1
Fujian Medical University, Fuzhou, 350108, Fujian Province, China.
2
Department of Radiation Oncology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, 350011, Fujian Province, China.
3
Laboratory of Immuno-Oncology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, 350011, Fujian Province, China.
4
Department of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY, 10029, USA.
5
State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology and the Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong, SAR, China.
6
Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, 350014, Fujian, China.
7
Department of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY, 10029, USA. bin.zhang@mssm.edu.
8
Department of Radiation Oncology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, 350011, Fujian Province, China. panjianji1956@163.com.

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.

KEYWORDS:

EBV-miR-BART8-3p; Epithelial-mesenchymal transition; Epstein-Barr virus; Erk1/2 signaling; Metastasis; NF-κB signaling; Nasopharyngeal carcinoma

PMID:
30477559
PMCID:
PMC6257964
DOI:
10.1186/s13046-018-0953-6
[Indexed for MEDLINE]
Free PMC Article

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