Effects of human and Epstein-Barr virus (EBV) non-coding RNAs (ncRNAs) on immortalized cells derived from nasopharyngeal epithelium in vitro

• Grant number: 17/23393-9
• Support Opportunities: Regular Research Grants
• Duration: August 01, 2018 - October 31, 2020
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Deilson Elgui de Oliveira
• Grantee: Deilson Elgui de Oliveira
• Host Institution: Instituto de Biotecnologia (IBTEC). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

EBV infection is implicated in the pathogenesis of proliferative disorders and various human cancers, notably the endemic form of Burkitt's Lymphoma and the undifferentiated variant of nasopharyngeal carcinoma. EBV was the first virus in which small non-coding RNAs (miRs) were found encoded in the viral genome. On the other hand, in the last two decades it has been verified that human endogenous miRs play an important role in carcinogenesis. Therefore, besides being influenced by human miRs, the development of human cancers associated with EBV infection may also be influenced by viral miRs. The present study aims to verify whether changes in the expression levels of certain human endogenous miRs or EBV miR-BARTs in human immortalized nasopharyngeal epithelial cells (INECs) modify their biological properties and in vitro behavior, favoring cell transformation or the acquisition of characteristics related to the biological aggressiveness of cancers. For this intent, primarily models based on EBV-negative INECs with altered expression of human endogenous miRs (miR-100, miR-192 and miR-574) and INECs infected by EBV with genomic deletion of miR-BARTs (miR-BART 7 and 9) by CRISPR/Cas9 will be stablished. Following, these EBV-positive and negative INECs will be evaluated in vitro for cell proliferation, cell transformation, migration and invasion, and. Molecular alterations underlying the possibly verified effects on ICES with altered expression of endogenous (EBV-negative) or viral miR-BARTs (EBV-positive) miRs will also be assessed for modulation of relevant intracellular signaling pathways in carcinogenesis, such as NF-ºB, PI3K/AKT, and JAK/STAT. (AU)