Latent membrane protein-1 of Epstein-Barr virus induces the expression of B-cell integration cluster, a precursor form of microRNA-155, in B lymphoma cell lines

miR-155, a microRNA, and its precursor form, B-cell integration cluster (BIC), are involved in tumor growth. Epstein-Barr virus (EBV)-associated malignancies are categorized into three types, based on their latent gene expression pattern: latency I, II, and III. In the present study, we found that infection with EBV increased the expression of BIC; in addition, substantial expression of BIC/miR-155 was detected in latency III-, but not in latency I-type cells. In comparison, latent membrane protein-1 (LMP1) was expressed in latency III-type cells. When LMP1 was over-expressed, BIC expression increased, indicating LMP1 mediates BIC expression. LMP1 is a membrane-associated protein known to activate signaling pathways. With the use of pathway inhibitors, we found that LMP1-induced strong BIC expression, primarily through NF-κB and p38/MAPK pathways. These results suggest that BIC/miR-155 play a role in lymphomagenesis through NF-κB and p38/MAPK pathways in response to activation by EBV LMP1.