Epstein-Barr virus infection induces miR-21 in terminally differentiated malignant B cells

The association of Epstein-Barr virus (EBV) with plasmacytoid malignancies is now well established but how the virus influences microRNA expression in such cells is not known. We have used multiple myeloma (MM) cell lines to address this issue and find that an oncomiR, miR-21 is induced after in vitro EBV infection. The PU.1 binding site in miR-21 promoter was essential for its activation by the virus. In accordance with its noted oncogenic functions, miR-21 induction in EBV infected MM cells caused downregulation of p21 and an increase in cyclin D3 expression. EBV infected MM cells were highly tumorigenic in SCID mice. Given the importance of miR-21 in plasmacytoid malignancies, our findings that EBV could further exacerbate the disease by inducing miR-21 has interesting implications both in terms of diagnosis and future miR based therapeutical approaches for the virus associated plasmacytoid tumors. What's new? Epstein-Barr virus (EBV) infection is ubiquitous in human populations, but the virus association with plasma cell malignancies is frequent in immunocompromised individuals. Furthermore, the mechanisms by which EBV may influence neoplastic transformation in such individuals remain unclear. Here, in multiple myeloma cell lines, EBV infection was found to induce the expression of miR-21, a microRNA which is frequently overexpressed in tumors. MiR-21 induction was associated with downregulation of p21, and EBV-infected cells readily produced tumors in SCID mice. The findings suggest that knowledge of miRNA profiles could be of diagnostic and therapeutic relevance in EBV associated plasmacytoid malignancies.