LMP1-miR-146a-CXCR4 axis regulates cell proliferation, apoptosis and metastasis

Epstein-Barr virus (EBV), the first human tumor virus to have been discovered, sustains an asymptomatic lifelong infection in ∼95% of the world's population. Reportedly, EBV infection induces the expression of specific cellular microRNAs (miRNAs), such as miR-155, miR-146a, miR-21, which can contribute to the persistence of latently infected cells. In this study, we investigated whether C-X-C chemokine receptor type 4 (CXCR4) is a cellular target of human miR-146a. We also investigated the role of miR-146a and CXCR4 in EBV-associated cells. The results indicate that miR-146a is more abundantly expressed in EBV-positive than in EBV-negative cells. MiR-146a down-regulated CXCR4 expression in a dose- and time-dependent manner. Phenotypic experiments detected miR-146a mimics that could suppress cell proliferation and cell migration and promote cell apoptosis by targeting CXCR4. In addition, miR-146a mimics suppressed cell survival by decreasing the population of G0/G1 phase cells. Latent membrane protein (LMP)1, an importance oncoprotein, can stimulate miR-146a and inhibit the CXCR4 expression. Our findings indicate that LMP1-miR-146a-CXCR4 axis functions as a regulator in the EBV-associated cells.