The role of lncRNA in melanoma progression

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

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PESSOA, DIOGO DE OLIVEIRA; RIUS, FLAVIA EICHEMBERGER; ANGELO PAPAIZ, DEBORA D.; PEDROSO AYUB, ANA LUISA; MORAIS, ALICE SANTANA; DE SOUZA, CAMILA FERREIRA; DA PAIXAO, VINICIUS FERREIRA; SETUBAL, JOAO CARLOS; NEWTON-BISHOP, JULIA; NSENGIMANA, JEREMIE; et al. Transcriptional signatures underlying dynamic phenotypic switching and novel disease biomarkers in a linear cellular model of melanoma progression. Neoplasia, v. 23, n. 4, p. 439-455, APR 2021. (17/25321-5, 19/05641-0, 18/20775-0, 14/01168-5, 11/18959-7, 14/13663-0)

PESSOA, DIOGO DE OLIVEIRA; RIUS, FLAVIA EICHEMBERGER; ANGELO PAPAIZ, DEBORA D.; PEDROSO AYUB, ANA LUISA; MORAIS, ALICE SANTANA; DE SOUZA, CAMILA FERREIRA; DA PAIXAO, VINICIUS FERREIRA; SETUBAL, JOAO CARLOS; NEWTON-BISHOP, JULIA; NSENGIMANA, JEREMIE; et al. Transcriptional signatures underlying dynamic phenotypic switching and novel disease biomarkers in a linear cellular model of melanoma progression. NEOPLASIA, v. 23, n. 4, p. 17-pg., 2021-04-09. (11/18959-7, 17/25321-5, 14/01168-5, 18/20775-0, 14/13663-0, 19/05641-0)