Effects of Human Papilloma virus and Epstein-Barr virus oncoproteins on the regulation of RECKs promoter

• Grant number: 22/02240-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): August 01, 2022
• Effective date (End): March 31, 2026
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Enrique Mario Boccardo Pierulivo
• Grantee: Beatrice Adrianne Silva Jorge
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The Human Papilloma Virus (HPV) and the Epstein-Barr Virus (EBV) are two important viruses classified as carcinogenic. Thirteen types of HPV known as high-risk HPV are associated with virtually all cases of Cervical Cancer. In fact, HPV types 16 and 18 are responsible for 70% of cases of this tumor. The HPV proteins E6 and E7 are the main products that lead to cell transformation, both are associated with the regulation of cell cycle, apoptosis and immune response. The EBV is related to nasopharyngeal and stomach carcinomas, as well as Burkitt's, non-Hodgkin's and Hodgkin's Lymphomas. The main oncogenic product of EBV is the LMP1 protein, whose function is to activate the Nf-ºB signaling pathway. Extracellular matrix remodeling plays a central role in carcinogenesis, leading to changes in the expression and activity levels of different proteins, one example is alterations in the metalloproteinase inhibitor, known as RECK. Previous group's works showed that the HPV E6 and E7 oncoproteins inhibit the expression of RECK, and the same result was seen in the presence of EBV LMP1. Despite the existence of a relationship, the mechanism by which this occurs is not yet known, by that, the present study aims to clarify how viral oncoproteins modulate RECK levels. For this, vectors that express viral oncoproteins with alterations in different functional domains will be used to determine which are important in the functional interaction with RECK. In addition, an in silico analysis will be performed to evaluate binding sites in the RECK promoter region that interacts with transcription factors. Finally, functional tests will be carried out to validate the previous observations. (AU)