Abstract
The metastasis of nasopharyngeal carcinoma (NPC) is a complex process associated with oncogenic dysfunction, the deciphering of which remains a challenge and requires more in-depth studies. Y-box protein 3 (YBX3) is a DNA/RNA binding protein associated with gene transcription, DNA repair, and the progression of various diseases. However, whether and how YBX3 affects the metastasis of NPC remains unknown. Thus, in this study, we aimed to investigate the role of YBX3 in the metastasis of NPC and determine its underlying mechanism. Interestingly, it was found that the expression of YBX3, which was associated with NPC metastasis, was upregulated in the clinical NPC tissues and cell lines. Moreover, we found that knockdown of YBX3 expression by lentivirus shRNA significantly suppressed NPC cells migration in vitro and metastasis in vivo. Mechanistically, RNA sequencing results suggested that the genes regulated by YBX3 were significantly enriched in cell adhesion molecules, cAMP signaling pathway, calcium signaling pathway, focal adhesion, PI3K/AKT signaling pathway, Ras signaling pathway, Rap1 signaling pathway, NF-κB signaling pathway, and Chemokine signaling pathway. Of these, PI3K/AKT signaling pathway contained the most genes. Accordingly, YBX3 knockdown decreased the activation of PI3K/AKT signaling pathway, thereby inhibit epithelial-to-mesenchymal transition (EMT) and MMP1. These results have demonstrated that YBX3 are involved in the metastasis of NPC through regulating PI3K/AKT signaling pathway, and serve as a potential therapeutic target for patients with NPC.
Highlights
Nasopharyngeal carcinoma (NPC) is a head and neck tumor whose incidence is higher in Southern China, Mediterranean Africa and the Middle East [1,2,3]
WB and QPCR analysis of fresh-frozen clinical samples showed that the protein and mRNA expressions of Ybox protein 3 (YBX3) were markedly upregulated in NPC tissues, compared to their expression in the normal nasopharyngeal tissues (Figures 1B, C)
S18, compared with that noted in the human normal nasopharyngeal epithelial cell NP460 (Figures 1E, F). These findings suggested that YBX3 expression levels were increased in NPC tissues and the 5-8F and S18 cells with the high malignancy and metastasis
Summary
Nasopharyngeal carcinoma (NPC) is a head and neck tumor whose incidence is higher in Southern China, Mediterranean Africa and the Middle East [1,2,3]. Previous studies suggested that the metastasis of NPC is a complex process that involves a number of factors and cell signaling pathways [7, 8]. Ybox protein family have diverse functions, such as regulation of transcription, splicing, translation, and mRNA stability [10, 11]. YBX3 is ubiquitous expressed in human skeletal muscle, heart, and decidual cells, which is thought to a multifunctional epithelialspecific protein involved in gene transcription, DNA repair, and interaction with other proteins [14]. Previous studies have demonstrated that YBX3 plays a role in gene transcription and translation of target genes that involved in cell survival, proliferation, and differentiation [15, 16]. The gene expression, biological functions, and prognostic values of YBX3 in NPC metastasis are still not clearly understood
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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
