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Epstein‐Barr virus (EBV) is a tumorigenic virus that can cause various human malignancies such as nasopharyngeal carcinoma (NPC) and gastric cancer (GC). EBV encodes 44 mature micro (mi)RNAs, mostly exhibiting oncogenic properties and promoting cancer progression. However, we have previously found that one EBV‐encoded miRNA, namely EBV‐miR‐BART6‐3p, acts as a tumor suppressor by inhibiting metastasis and invasion. Here, we report that EBV‐miR‐BART6‐3p inhibits the proliferation of EBV‐associated cancers, NPC, and GC, by targeting and downregulating a long non‐coding RNA (lncRNA), LOC553103. Through proteomics analysis, we determined that stathmin (STMN1) is affected by EBV‐miR‐BART6‐3p and LOC553103. Further, via RNA immunoprecipitation and luciferase reporter assay, we confirmed that LOC553103 directly binds and stabilizes the 3′UTR region of STMN1 mRNA. These results indicate that the EBV‐miR‐BART6‐3p/LOC553103/STMN1 axis regulates the expression of cell cycle‐associated proteins, which then inhibit EBV‐associated tumor cell proliferation. These findings provide potential targets or strategies for novel EBV‐related cancer treatments, as well as contributes new insights into the understanding of EBV infection‐related carcinogenesis. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is a unique EBV‐associated subtype of head and neck cancer, which has the highest incidence in Southern China and eastern South Asia. The interaction between genetic risk factors and environmental challenge, have been considered to contribute to the development of nasopharyngeal carcinogenesis. Constitutive activation of NF‐κB signaling has been seen in NPC tissues and is associated with unfavorable prognosis. Recently, several whole exome sequencing study consistently revealed that high frequency mutations of NF‐κB pathway negative regulators is common in nasopharyngeal carcinoma, which reinforce the importance of NF‐κB driving oncogenesis. This review focuses on the current state of research in role of NF‐κB in NPC carcinogenesis. We summarized the newly identified loss of function (LOF) mutations on NF‐κB negative regulators leading to it's activation bypass LMP‐1 stimulation. We discussed the critical role of NF‐κB activation in immortalization and transformation of nasopharygeal epithelium. We also depicted how NF‐κB signaling mediated chronic inflammation contribute to persistent EBV infection, immune evasion of EBV infected cells, metabolic reprogramming, and cancer stem cells (CSCs) formation in NPC. Lastly, we discussed the clinical resonance of targeting NF‐κB for NPC precise therapy. [ABSTRACT FROM AUTHOR]