Exploring NRF2 and its target genes from a ferroptotic perspective in tumor cell lines

• Grant number: 23/15341-0
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: March 11, 2024
• End date: July 10, 2024
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Clarissa Ribeiro Reily Rocha
• Grantee: Izabela Amelia Marques de Andrade
• Supervisor: Jose Pedro Friedmann Angeli
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Institution abroad: Julius-Maximilians-Universität Würzburg (JMU), Germany
• Associated to the scholarship: 22/14035-0 - Comparison between 2D and 3D model in the response to ferroptosis and chemotherapy of tumor cells, BP.IC

Abstract

Cancer is one of the major causes of death today, and its treatment is a worldwide concern. Although many advances have been made in this area, the emergence of resistance is quite frequent favoring the disease's fatality. This process is closely associated with cell regulation systems, which are central in terms of therapeutic targets. In this sense, NRF2 is a transcription factor, involved in antioxidant response modulation, has been described to be highly active in a variety of tumors, and is intrinsically related to resistance phenotypes. It is also involved in the processes that lead to ferroptosis, a type of cell death marked by iron and lipid ROS dependency. However, it has been shown that NRF2 may play a dual role in ferroptosis once it induces genes that are important to promote or inhibit this type of cell death. The present study aims to contribute to a better understanding of the role of NRF2 in the modulation of ferroptosis, through the utilization of a customized CRISPR knockout library. We believe that this will allow a more precise evaluation of genes involved in this puzzle, hopefully leading to more efficient treatment for the patients.