Effects in vitro of Epstein-Barr oncoprotein LMP1 on endogenous microRNA expression and invasion of human carcinoma cells

Abstract

The Epstein-Barr vírus (EBV) is an ubiquitous herpesvirus that participates in the pathogenesis of many human cancers, such as the endemic Burkitt lymphoma and the undifferentiated nasopharyngeal carcinoma. EBV has tropism for B lymphocytes and epithelial cells, and the viral cycle is divided into the lytic and latent infection phases. Distinct viral strains may present peculiar biological properties: compared to the viral isolate B95-8, M81 has propensity to infect epithelial cells and it is more likely to induce spontaneous lytic activation. In latently-infected neoplastic cells, the EBV express a limited set of viral products, and some of them have well documented oncogenic properties. In this regard, the viral latent membrane protein 1 (LMP1) is worthy to note. LMP1 is a transmembrane protein with transforming properties both in vitro and in vivo. Furthermore, epithelial cells expressing LMP1 show increased cell mobility and invasion, with impact on the biological behavior of EBV-associated carcinomas. LMP1 regulates the expression of some cellular microRNAs, including members of the miR-200 family and the miR-21. The miR-200 microRNAs regulates the maintenance of epithelial features and it is frequently suppressed in carcinomas. On the other hand, miR-21 stimulates cell proliferation, cell migration and invasion, and it is very often overexpressed in cancers. Though it is reported that the expression of EBV LMP1 contributes to the metastatic potential of nasopharyngeal carcinomas, it is unknown whether different viral LMP1 forms have distinct effects on the progression of carcinomas. Therefore, this aims to verify whether the LMP1 from B95-8 and M81 EBV isolates behaves distinctly regarding cell invasion and the expression of miR-200 and miR-21 cellular microRNAs. For this intent, carcinoma cells expressing the LMP1 protein from B95-8 and M81 will be produced, and they will be subjected to in vitro cell invasion assay as well as miRNAs expression analysis, in order to verify potential differences between the viral isolates evaluated. (AU)