YBX3 Mediates the Metastasis of Nasopharyngeal Carcinoma via PI3K/AKT Signaling

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.

High-Frequency Irreversible Electroporation (H-FIRE) Induced Blood–Brain Barrier Disruption Is Mediated by Cytoskeletal Remodeling and Changes in Tight Junction Protein Regulation

“…Intracellular Adhesion Molecule 1 ( Icam1 ), Y-box Binding Protein 3 ( Ybx3 ), Ras-related C3 Botulinum Toxin Substrate 1 ( Rac1 ) and Glycogen Synthase Kinase-3 beta ( Gsk3b ) gene expression was significantly increased following intracranial H-FIRE. YBX3 functions as a DNA/RNA binding protein that regulates transcription, translation and DNA repair; thus, the increase in gene expression observed is not surprising given the impact intracranial H-FIRE has on gene regulation [ 58 ]. ICAM1 is expressed on brain endothelial cells and plays a major role in immune cell trafficking; thus, H-FIRE appears capable of facilitating local immune cell infiltration [ 59 ].…”

Roles of GFPT2 Expression Levels on the Prognosis and Tumor Microenvironment of Colon Cancer

“…Focal adhesion kinases (FAKs) are a class of cytoplasmic non-receptor protein tyrosine kinases that belong to the protein tyrosine kinase (PTK) superfamily and are therefore also known as PTK II (32). FAKs can integrate signals from integrins, growth factors and mechanical stimuli to activate intracellular PI3K/Akt, Ras/MAPK and other signaling pathways to regulate cell growth (33)(34)(35). Numerous studies on the association of FAKs with different types of cancers have shown a close link between FAKs and the biological mechanisms that promote cancer development and progression (36).…”

Lipocalin 2 Reduces MET Levels by Inhibiting MEK/ERK Signaling to Inhibit Nasopharyngeal Carcinoma Cell Migration

“…Elevated serum c-Src levels are associated with a poor prognosis in NPC patients [ 44 ]. The expression of YBX3 is positively correlated with NPC metastasis [ 45 ]. An abnormal expression of COX-2 is associated with recurrence and a poor prognosis in NPC patients [ 46 ].…”