Analysis of the role of lncRNAs with prognostic value in Melanoma progression

• Grant number: 21/06214-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2021
• End date: November 30, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Miriam Galvonas Jasiulionis
• Grantee: Beatriz Cristina Biz Tonin
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Long non-coding RNAs (lncRNAs) are non-protein-coding RNAs (ncRNAs) and represent the majority of transcripts. It is estimated that 70 to 90% of the human genome is transcribed in ncRNA. Studies have already demonstrated the importance of ncRNAs in modulating gene expression, which is considered an important piece of the epigenetic machinery. LncRNAs participate in the regulation of cell proliferation, migration, and differentiation and, in this way, are related to many diseases, such as cancer. Melanoma is the most lethal skin cancer, responsible for about 80% of deaths from this cancer. This is because it has a high probability of metastasizing and is very resistant to treatments. Our laboratory has developed a linear model of melanoma progression based on sequential cycles of deadhesion-adhesion of a murine lineage of non-tumorigenic melanocytes, melan-a, which resulted in the malignant transformation and originated progressively more aggressive cell lines. With this model, we can study melanoma at various stages of its progression, from non-tumorigenic cells (melan-a) to cells with high metastatic potential (4C11+). For this work, we used four cell lines, melan-a (melanocytes), 4C (pre-malignant melanocytes), 4C11- (undifferentiated, non-metastatic melanoma cells) and 4C11+ (differentiated, highly proliferative, and metastatic melanoma cells), which were analyzed for the expression profile of lncRNAs. Preliminary analyzes considering the proximity to lncRNAs and expression pattern were performed and, with this, sixteen differentially expressed genes were chosen in the model that has their gene expression potentially related to the expression of the neighboring lncRNA. In this project, we will analyze the lncRNAs that may possibly be related to these sixteen genes, in order to identify the role of lncRNAs in their expression and to determine their influence on the behavior of melanoma cells. This study may reveal important lncRNAs for the biology of melanoma, in addition to possibly indicating its use as a prognostic biomarker.(AU)