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MicroRNAs (miRNAs) regulate gene expression to participate in carcinogenesis and tumor progression. Therefore, identification of a malignant phenotype associated with miRNAs and therapeutic targets will contribute substantially in improving nasopharyngeal carcinoma (NPC) treatment. In this study, we demonstrated that overexpression of let-7i-5p promotes the malignant phenotype by acting as an autophagy suppressor by targeting ATG10 and ATG16L1 in NPC. Expression levels of let-7i-5p were markedly increased in NPC and head and neck cancers based on an analysis of the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Using a cohort comprising 150 NPC tissues, we found that let-7i-5p was correlated with advanced stage, recurrence, metastasis, lymph node metastasis, and poor clinical outcomes. In addition to a series of in vitro cellular analyses, in vivo mouse tumor models revealed that let-7i-5p inhibits autophagy and promotes the malignant phenotype of NPC by targeting ATG10 and ATG16L1. Our findings demonstrate that let-7i-5p may represent a promising therapeutic target for NPC treatment.

Vascular mimicry (VM) is defined as a vascular channel-like structure composed of tumor cells that correlates with the growth of cancer cells by providing blood circulation. However, whether VM can be formed in dormant cancer cells remains unclear. Our previous research revealed that polyploid giant cancer cells (PGCCs) are specific dormant cells related to the poor prognosis of head and neck cancer. Here, we demonstrated that EBV could promote VM formation by PGCCs in vivo and in vitro. Furthermore, we revealed that the activation of the ERK pathway partly mediated by LMP2A is responsible for stemness, and the acquisition of the stemness phenotype is crucial to the malignant biological behavior of PGCCs. The epithelial-to-mesenchymal transition (EMT) process plays a considerable role in PGCCs, and EMT progression is vital for EBV-positive PGCCs to form VM. This is the first study to reveal that EBV creates plasticity in PGCC-VM and provide a new strategy for targeted anti-tumor therapy.