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The role of lncRNA in melanoma progression

Grant number: 17/25321-5
Support type:Scholarships in Brazil - Master
Effective date (Start): April 01, 2018
Effective date (End): July 31, 2019
Field of knowledge:Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Miriam Galvonas Jasiulionis
Grantee:Ana Luisa Pedroso Ayub
Home Institution: Instituto Nacional de Farmacologia (INFAR). Universidade Federal de São Paulo (UNIFESP). São Paulo , SP, Brazil

Abstract

It is estimated that around 90% of the genome is transcribed into non-coding RNA (ncRNA). The ncRNAs can be divided into small and long ncRNAs. The long ncRNAs (LncRNA) have been previously shown to participate in biological processes such as proliferation, differentiation and cellular migration, and changes in their expressions have been associated to several diseases, including cancer. Furthermore, recent studies show that LncRNA can regulate the epigenetics machinery through chromatin silencing and remodeling. Melanoma is one of the most aggressive types of cancer, developing high probability of metastasis and showing an unfavorable response to therapies. Our lab has developed a model of melanoma progression, in which different cell lines represent distinct stages of the progression model, as nontumorigenic melanocytes were exposed to sustained stressed conditions (cycles of adhesion blockage). Evaluating the RNA sequencing results of the 4 cell lines of this model (melan-a, nontumorigenic melanocytes: 4C; premalignant melanocytes: 4C11-; non-metastatic melanoma cells; 4C11+, metastatic melanoma cells), we have identified 3032 genes which displayed differentiated expression levels, out of which 6 were selected, being 5 LncRNAs: HOTAIR, Fendrr, MIR670Hg, Nespas and Dlx4os and the Dlx4 gene. With this work, we aim to investigate those 6 genes differently expressed during melanoma progression, through functional assays in vitro and tumorigenicity assay in vivo. The results could be used as the foundation for new prognostics techniques, diagnostic and melanoma therapy, at the same time as it may contribute to a better understanding of the role of LncRNAS on the melanoma genesis and progression. (AU)