科研之友
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摘要
The development and progression of nasopharyngeal carcinoma (NPC) is closely associated with Epstein-Barr virus (EBV) infection. NPC is usually asymptomatic until it spreads to other sites, and more than 70% of cases are classified as locally advanced disease at diagnosis. EBV-positive nasopharyngeal cancer tissues express only limited viral latent proteins, but express high levels of the EBV-encoded BamHI-A right-rotation microRNA (BART miRNA) molecules. Here, we report that EBV-microRNA-BART2-5p (BART2-5p) promotes NPC cell invasion and metastasis in vivo and in vitro, but has no effect on NPC cell proliferation and apoptosis. In addition, BART2-5p significantly altered the mRNA and microRNA expression profiles of NPC cells. The development of human tumors has been reported to be associated with altered microRNAs expression and overall microRNAs expression is reduced in many types of tumors. We found that BART2-5p downregulated the expression of several microRNAs that could exert oncogenic functions. Mechanistically, BART2-5p directly targets the RNase III endonuclease DICER1, inhibiting its function of cleaving double-stranded stem-loop RNA into short double-stranded RNA, which in turn causes altered expression of a series of key epithelial-mesenchymal transition (EMT) molecules, and reverting DICER1 expression can rescue this phenotype. Furthermore, analysis from clinical samples showed a negative correlation between BART2-5p and DICER1 expression. According to our study, high expression of BART2-5p in tissues and plasma of patients with NPC is associated with poor prognosis. Our results suggest that, EBV-encoded microRNA BART2-5p can accelerates NPC metastasis through modulating microRNA profiles which are mediated by DICER1, implying a novel role of EBV microRNAs in the pathogenesis of NPC.
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