Identification and analysis of the role of lncRNAs in melanoma development and resistance to immunotherapies

• Grant number: 24/20708-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2025
• End date: May 31, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Miriam Galvonas Jasiulionis
• Grantee: Guilherme Gabriel Vicêncio
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Melanoma is the most lethal type of skin cancer due to its high metastatic capacity and frequent resistance to available treatments. Targeted therapies and immunotherapies, including immune checkpoint inhibitors, although currently considered gold standard treatment options, are associated with response failure or resistance in around half of melanoma patients. Therefore, the search for new targets and therapeutic strategies remains necessary. Long non-coding RNAs (lncRNAs) are vital in biological processes such as the regulation of gene expression. Several studies have shown the role of lncRNAs both in regulating immune responses and in the development and progression of melanoma. However, although there are studies showing this relationship, knowledge about the role of lncRNAs in the response of melanoma to treatment with immune checkpoint inhibitors is still very limited. For this work, we used as a basis the cell lines of the melanoma progression cell model developed in our laboratory, which is made up of four lines, melan-a (melanocytes), 4C (pre-malignant melanocytes), 4C11- (undifferentiated, slow-growing and non-metastatic melanoma cells) and 4C11+ (differentiated, highly proliferative and metastatic melanoma cells). Based on these cell lines, an analysis was carried out which identified genes whose expression is altered during the development of melanoma and which are correlated with immune infiltration. From this, we will evaluate the lncRNAs close to these genes and, from this in silico analysis, we will characterize the chosen lncRNAs and their relationship with the response of melanoma to immunotherapies. The project will aim to cover part of this knowledge gap about the role of lncRNAs in the development of melanoma and its response to immunotherapies.