MELANOPSIN'S PARTICIPATION IN PROTECTION AGAINST CELL DEATH: ROLE IN MELANOMA TUMORIGENESIS

• Grant number: 23/01944-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2023
• End date: July 31, 2024
• Field of knowledge: Biological Sciences - Physiology
• Principal Investigator: Maria Nathália de Carvalho Magalhães Moraes Figueira Borges
• Grantee: Maria Eduarda Palma Savini
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
• Associated research grant: 17/26651-9 - Glaucoma as a model of temporal information disruption: impact on the metabolism, AP.JP

Abstract

Melanoma is a skin cancer caused by the accelerated growth of melanocytes due to activation of oncogenes or inactivation of suppressor genes. Its incidence has increased worldwide, and its mortality corresponds to approximately 80% of diagnosed cases. Several factors contribute to the melanoma development, such as genetic mutations, changes in the tumor microenvironment and suppression of the immune response. In addition, exposure to UV radiation also contributes to the progression of the disease, altering signaling pathways related to tumor cell proliferation, growth, and resistance to apoptosis. The absorption of UV rays and visible light takes place by a photoreception system that converts light into electrical signals in the presence of specialized proteins called opsins, making a connection between the external environment and the regulation of the body's responses to light. This system is present in the retina, being responsible for image formation and regulation of the biological clock, and in the skin, function as a light, UVA radiation and temperature sensor, with melanopsin (OPN4) being the main opsin involved. The melanopsin, present in fibroblasts, keratinocytes and melanocytes (skin cells), is also linked to several other non-photic factors such as cell proliferation, apoptosis and control of the amount of melanin present in the cell, mainly in melanocytes(normal or malignant). According to studies, in malignant melanocytes the presence of melanopsin promotes an immunosuppressive tumor microenvironment, faster proliferation, increases GTPase activity and leads to a reduction in cell death, thus acting as a tumor oncogene. Considering the action of OPN4 on malignant melanocytes, this project aims to evaluate the role of melanopsin in protecting against cell death induced by oxidative stress in murine melanoma. For this, we will use a culture of tumor melanocytes that were genomic editing by CRISPR and express the non-functional melanopsin. Then, we will perform cell death assays induced by hydrogen peroxide treatment and we will evaluate the apoptosis and necroptosis pathways through analysis of gene expression by real time PCR and cell viability by flow cytometry.