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

TitleEBV-miR-BART8-3p induces epithelial-mesenchymal transition and promotes metastasis of nasopharyngeal carcinoma cells through activating NF-κB and Erk1/2 pathways
Authors
KeywordsEBV-miR-BART8-3p
Epithelial-mesenchymal transition
Epstein-Barr virus
Erk1/2 signaling
Metastasis
Nasopharyngeal carcinoma
NF-κB signaling
Issue Date2018
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.jeccr.com/home
Citation
Journal of Experimental and Clinical Cancer Research, 2018, v. 37, article no. 283 How to Cite?
AbstractBackground: 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.
Persistent Identifierhttp://hdl.handle.net/10722/272006
ISSN
2017 Impact Factor: 6.217
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLin, C-
dc.contributor.authorZong, J-
dc.contributor.authorLin, W-
dc.contributor.authorWang, M-
dc.contributor.authorXu, Y-
dc.contributor.authorZhou, R-
dc.contributor.authorLin, S-
dc.contributor.authorGuo, Q-
dc.contributor.authorChen, H-
dc.contributor.authorYe, Y-
dc.contributor.authorZhang, B-
dc.contributor.authorPan, J-
dc.date.accessioned2019-07-20T10:33:51Z-
dc.date.available2019-07-20T10:33:51Z-
dc.date.issued2018-
dc.identifier.citationJournal of Experimental and Clinical Cancer Research, 2018, v. 37, article no. 283-
dc.identifier.issn1756-9966-
dc.identifier.urihttp://hdl.handle.net/10722/272006-
dc.description.abstractBackground: 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.-
dc.languageeng-
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.jeccr.com/home-
dc.relation.ispartofJournal of Experimental and Clinical Cancer Research-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectEBV-miR-BART8-3p-
dc.subjectEpithelial-mesenchymal transition-
dc.subjectEpstein-Barr virus-
dc.subjectErk1/2 signaling-
dc.subjectMetastasis-
dc.subjectNasopharyngeal carcinoma-
dc.subjectNF-κB signaling-
dc.titleEBV-miR-BART8-3p induces epithelial-mesenchymal transition and promotes metastasis of nasopharyngeal carcinoma cells through activating NF-κB and Erk1/2 pathways-
dc.typeArticle-
dc.identifier.emailChen, H: hlchen@hku.hk-
dc.identifier.authorityChen, H=rp00383-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1186/s13046-018-0953-6-
dc.identifier.pmid30477559-
dc.identifier.pmcidPMC6257964-
dc.identifier.scopuseid_2-s2.0-85057175659-
dc.identifier.hkuros298560-
dc.identifier.volume37-
dc.identifier.spagearticle no. 283-
dc.identifier.epagearticle no. 283-
dc.identifier.isiWOS:000451326300004-
dc.publisher.placeUnited Kingdom-

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