Modulation of the microRNA cluster miR-183-96-182 expression by the Epstein-Barr virus latent membrane protein 1. Homo sapiens

Epstein-Barr virus (EBV) is an oncogenic human herpesvirus involved in the pathogenesis of Burkitt’s lymphoma (BL) and various other lymphoproliferative disorders. In BL, EBV protein expression is restricted to the EBNA-1, but small non-coding RNAs such as the EBERs and micro (mi)RNAs can also be detected. miRNAs play major roles in crucial processes such as proliferation, differentiation and cell death. It has recently become clear that alteration in the expression profile of miRNAs contribute to the pathogenesis of a number of malignancies. During latent infection, EBV expresses 25 viral pre-miRNAs and modulates the expression of specific cellular miRNAs, such as miR-155 and miR-146, which potentially play a role in oncogenesis. Here, we established the small RNA expression profiles of three BL cell lines. Using large-scale sequencing coupled to northern blot and real-time RT-PCR analysis validation, we demonstrated the differential expression of some cellular and viral miRNAs. High-level expression of the miR-183-96-182 cluster and EBV miR-BART cluster was significantly associated with EBV type I latency. This expression was not affected by viral reactivation since TGF-ß1 stimulation did not significantly change the miRNA profiles. However, the expression of latent membrane protein (LMP)-1 triggered down-regulation of the expression of the miR-183-96-182 cluster. We further show that this effect involves the AKT signaling pathway. Overall design: Cellular and viral miRNA profiling of the EBV-positive Burkitt's lymphoma (BL) cell lines Mutu, Kem and Sav treated (2h and 24h post-treatment) or not (0h) with TGF-β1 Please note that EBV-positive BL cell lines can be classified into 3 different latency types, termed latency I to III, based on the expression pattern of several EBV latent genes. Our Mutu and Kem cells were in latency I as expected, and are therefore referred to as Mutu-I and Kem-I in our study. However, our Sav cells appeared to have derived from a type I latency to a latency type not yet characterized. Therfore, the Sav cells were refered as Sav* cells and the '*' value was provided in the corresponding characteristics field.