Recently, super-enhancers (SEs) have been identified as a unique type of transcriptional regulation involved in cancer development. SEs exhibit a size, high transcription factor density, and strong binding to the transcriptional machinery compared with typical enhancers. SEs play an essential role in cell growth, differentiation, and disease initiation and progression including tumorigenesis. In particular, cancer-specific SEs have been proven to be key oncogenic drivers types of tumor cells. Furthermore, it has been confirmed that cancer-specific SEs can mediate the dysregulation of signaling pathways and promote cancer cell growth. Additionally, therapeutic strategies directly targeting SE components, for example, by disrupting SE structure or inhibiting SE cofactors, have shown a good curative effect on various cancers.
Epstein-Barr virus (EBV) is a specific tumorigenic factor in the pathogenesis of nasopharyngeal carcinoma (NPC). Viral products encoded by EBV (LMP1, LMP2A, EBNA1, and miRNAs) have been shown to promote NPC metastasis. EBV-encoded oncoproteins and miRNAs have been shown to induce epithelial-mesenchymal transition (EMT) indirectly by inducing EMT transcription factors (EMT-TFs). These EBV-encoded products also promote the expression of EMT-TFs through post-transcriptional regulation. EMT contributes to generation of circulating tumor cells (CTCs) in epithelial cancers. CTCs exhibit stem cell characteristics, including increased invasiveness, enhanced cell intravasation, and improved cell survival in the peripheral system. EBV may contribute NPC metastasis through promoting generation of CTCs. Furthermore, CTC karyotypes are associated with NPC staging, therapeutic sensitivity, and resistance. We summarized studies showing that EBV-encoded virus-proteins and miRNAs promote generation of NPC CTCs, and highlighted the associated mechanism. This synthesis indicated that EBV mediates NPC metastasis through generation of CTCs.
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