Effects of epstein-barr virus LMP1 oncoprotein on in vitro cell invasion and expression of endogenous microRNAs in human cells

Author(s)

Barbara Grasiele Muller Coan

• Document type: Master's Dissertation
• Press: Botucatu. 2016-12-02.
• Institution: Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu
• Defense date: 2016-09-30
• Advisor: Deilson Elgui de Oliveira

Abstract

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus that participates in many human cancers pathogenesis, such as endemic Burkitt lymphoma and undifferentiated nasopharyngeal carcinoma. EBV cycle is divided into the lytic and latent infection and distinct viral strains may present peculiar biological properties; compared to the viral isolate B95-8, M81 has propensity to epithelial cell infection and can more likely induce spontaneous lytic activation. In latently-infected neoplastic cells, EBV expresses a limited set of viral products, some of them with well documented oncogenic properties, like latent membrane protein 1 (LMP1). 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 EBVassociated carcinomas. Cellular microRNAs are involve in many cellular processes like cell cicle progression, cell proliferation, cell metabolism and apoptosis. Some of those microRNAs are related to carcinogenesis, cancer progression and even resistance to chemotherapy drugs. Though EBV LMP1 expression can contribute to metastatic potential of nasopharyngeal carcinomas, it is unknown whether different viral LMP1 forms may have distinct effects on the progression of carcinomas. We verified if LMP1 from B95-8 or M81 EBV isolates behaves distinctly regarding cell migration, invasion and microRNA expression. For this intent, we used human cells expressing the LMP1 protein from EBV B95-8 and M81 strains, and performed in vitro cell invasion and migration assays as well as miRNAs expression analysis using rt-PCR. Regarding migration and invasion, both isolates showed similar results. However, microRNA expression pointed in silico evidence that M81, when compared to M81, can downregulate genes involved in focal adhesion, apoptosis escape, gene expression, cell motility and proliferation. (AU)

• FAPESP's process: 14/15678-5 - Effects in vitro of Epstein-Barr oncoprotein LMP1 on endogenous microRNA expression and invasion of human carcinoma cells
• Grantee: Barbara Grasiele Muller Coan
• Support Opportunities: Scholarships in Brazil - Master