Targeting ZFAND5 by EBV-encoded miR-BART19-3p drives malignant phenotypes in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated epithelial malignancy with distinct geographic distribution and a high propensity for local invasion and distant metastasis. EBV-encoded microRNAs have emerged as important viral regulators of host gene expression in NPC; however, the biological function of EBV-miR-BART19-3p remains incompletely understood. In this study, public transcriptomic and microRNA datasets were analyzed to identify dysregulated molecules in NPC, and ZFAND5 was predicted as a potential target of EBV-miR-BART19-3p. EBV-miR-BART19-3p was significantly upregulated in NPC tissues and EBV-positive C666-1 cells, whereas ZFAND5 was downregulated at both the mRNA and protein levels. Kaplan-Meier analysis further showed that higher ZFAND5 expression was associated with better disease-free survival in a public NPC cohort. Dual-luciferase reporter assays confirmed that EBV-miR-BART19-3p directly binds to the 3'-untranslated region of ZFAND5. Functionally, EBV-miR-BART19-3p overexpression enhanced C666-1 cell proliferation, colony formation, migration and invasion while suppressing apoptosis. Conversely, EBV-miR-BART19-3p inhibition or ZFAND5 overexpression suppressed these malignant phenotypes and promoted apoptosis. Importantly, ZFAND5 knockdown partially reversed the tumor-suppressive effects induced by EBV-miR-BART19-3p inhibition. Bioinformatic enrichment analysis indicated that differentially expressed genes in NPC were associated with immune regulation, chemokine signaling, cell adhesion, PI3K-Akt, Wnt and NF-kappaB signaling. These findings suggest that EBV-miR-BART19-3p promotes malignant phenotypes in EBV-positive NPC cells, at least in part, by repressing ZFAND5, providing a potential mechanistic link between EBV-encoded microRNAs and NPC progression.