Abstract
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-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.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-κB and Erk1/2 signaling pathways. Our findings suggest that EBV-miR-BART8-3p is a potential therapeutic target for NPC.
Highlights
Epstein-Barr virus (EBV) is ubiquitously associated with nasopharyngeal carcinoma (NPC)
The present study demonstrates that EBV-miR-BART8-3p plays a significant role in inducing epithelial-mesenchymal transition (EMT) and promoting metastasis through directly targeting RNF38 in NPC cells via the activation of NF-κB and Erk1/ 2 signaling pathways
We identified 30 downregulated miRNAs and 56 upregulated miRNAs in NPC versus control using the criteria of an fold change (FC) of > 1.2 and an false discovery rate (FDR) of < 0.05 (Fig. 1a; Additional file 1: Table S1)
Summary
Epstein-Barr virus (EBV) is ubiquitously associated with nasopharyngeal carcinoma (NPC). 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. NPC is rare worldwide [3], this malignancy remains highly prevalent in endemic regions, notably in southern China [4]. A set of EBV latent genes have been identified to play an important role in the development of NPC, including three latent membrane proteins (LMP1, LMP2A and LMP2B), EBV nuclear antigen 1 (EBNA1) and EBV-encoded RNAs (EBERs) [3]. Only three latent proteins (EBNA1, LMP1 and LMP2A) are expressed in type II latency of EBV infection, a predominant form of latency observed in NPC [4]. Whereas EBV-encoded microRNAs (EBV-miRNAs) are detected in most of clinical NPC specimens and cells during all the forms of latency [5,6,7,8]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call