Downregulation of miR-10b-3p by EBV promotes tumor growth and metastasis via ITGAV in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor strongly associated with Epstein-Barr virus (EBV) infection. EBV-mediated dysregulation of host microRNAs (miRNAs) contributes to NPC pathogenesis, but the functions of many EBV-regulated host miRNAs remain incompletely defined. miR-10b-3p is markedly downregulated in EBV-positive NPC, yet its biological significance and downstream mechanism remain unclear. Here, we found that miR-10b-3p was reduced in EBV-positive NPC tissues and was further suppressed following EBV infection of non-malignant nasopharyngeal epithelial cells and EBV-negative NPC cell lines. Restoration of miR-10b-3p expression markedly inhibited cell proliferation, colony formation, migration, invasion, and epithelial-mesenchymal transition (EMT) in EBV-positive NPC cells, whereas inhibition of miR-10b-3p in EBV-negative NPC cells produced the opposite effects. In nude mouse xenograft and lung metastasis models, overexpression of miR-10b-3p significantly reduced tumor growth and pulmonary metastasis. Mechanistically, miR-10b-3p directly targeted the 3'-UTR of integrin subunit alpha V (ITGAV), leading to decreased ITGAV expression and subsequent attenuation of STAT5 and ERK1/2 signaling. Forced ITGAV expression partially reversed the suppressive effects of miR-10b-3p on tumor cell proliferation, migration, invasion, and EMT. Moreover, miR-10b-3p levels were inversely correlated with ITGAV expression in NPC tissues. Collectively, these findings identify an EBV-regulated miR-10b-3p/ITGAV/STAT5-ERK1/2 axis in NPC and show that loss of miR-10b-3p promotes tumor growth and metastasis by relieving ITGAV repression, suggesting potential therapeutic targets for EBV-associated NPC.