Abstract
Accumulating evidence so far has shown that EBV's miRNAs have been found to be involved in cancer progression. However, the comprehensive EBV miRNA expression profiles and their biological significance in EBV-associated diseases are not well documented. A comprehensive profiling of EBV-encoded miRNAs expressed in CAEBV, EBV-HLH, and nasopharyngeal carcinoma (NPC) patients was constructed, and the results showed that miR-BART19-3p was upregulated in all these diseases. Ectopic expression of miR-BART19-3p induced EBV-negative cell proliferation and suppressed cell apoptosis. Molecularly, adenomatous polyposis coli (APC) was identified to be a direct target of miR-BART19-3p, and APC mRNA expression was inversely correlated with miR-BART19-3p in CAEBV samples. Our results demonstrated that miR-BART19-3p contributes to the tumorigenesis of EBV-associated diseases and may be a potential therapeutic target.
Highlights
Epstein-Barr virus (EBV), one of eight human herpesviruses, infects over 95% of the population worldwide
EBV is etiologically linked to several human malignancies, including Burkitt’s lymphoma (BL), undifferentiated nasopharyngeal carcinoma (NPC), and EBV-associated gastric carcinoma (EBVa GC) [1]
Among these miRNAs, we focused on miRBART19-3p due to the effects on cell growth (Figure 2(a))
Summary
Epstein-Barr virus (EBV), one of eight human herpesviruses, infects over 95% of the population worldwide. EBV persists lifelong as a latent infection in the B lymphoid system and maintains a finely balanced relationship with humans. EBV can infect T cells and NK cells and induce chronic active EBV infection (CAEBV) [3], EBV-associated hemophagocytic lymphohistiocytosis (EBVHLH) [4], and EBV-associated T/NK cell lymphoproliferative diseases [5]. CAEBV usually occurs following primary EBV infection and is mainly characterized by clonal proliferation of EBV-infected T/NK cells and inflammatory cytokine production [7]. The mechanism by which EBV induces proliferation of T/NK cells and cytokines has not been elucidated. EBV is etiologically linked to several human malignancies, including Burkitt’s lymphoma (BL), undifferentiated nasopharyngeal carcinoma (NPC), and EBV-associated gastric carcinoma (EBVa GC) [1]
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