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Non-coding RNAs involved with melanoma genesis and progression

Grant number: 18/20775-0
Support type:Regular Research Grants
Duration: July 01, 2019 - June 30, 2021
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Miriam Galvonas Jasiulionis
Grantee:Miriam Galvonas Jasiulionis
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated grant(s):19/23480-4 - Novel strategies for eliminating residual tumor cells using epigenetic therapy, AP.R SPRINT

Abstract

Melanomas are tumors that may frequently progress to their most aggressive form, the metastatic one, been responsible for more than 80% of deaths caused by all types of skin cancers. Considering that, if not early diagnosed and treated, it can rapidly progress and become fatal, the search for tumor markers in tumor samples and biological fluids has received increased attention. It is estimated that 90% of our genome are transcribed into non-coding RNAs (ncRNAs). NcRNAs, which include the micro RNAs (miRNAs) and long ncRNAs (lncRNAs), are among the frequent molecular alterations found in tumors, like melanomas. The role of lncRNAs has been described in processes such as cell proliferation, differentiation and migration. In addition, recent studies have demonstrated that lncRNAs can regulate the epigenetic machinery, splicing and mRNA stability, besides recruiting transcription factors. miRNAs have regulatory function and control several biological processes, since they bind to target mRNAs and impair their translation. The increased or decreased expression of ncRNAs contribute to the loss of cellular homeostasia and favor the onset of many diseases, include cancer. Besides their roles in tumor biology, studies have demonstrated the potential use of ncRNAs as markers for diagnosis, prediction of response to therapy, and prognosis to monitor disease progression. In this context, based on a linear cellular model of melanoma progression, our aim is to investigate and identify differentially expressed ncRNAs during melanoma progression, elucidate their functional roles in melanoma biology, and evaluate their potential to predict the evolution to metastasis, contributing to therapeutic decision. This study, initially based on a cellular model, will be validated in human melanoma cell lines and exosomes isolated from plasma of patients with primary melanomas, presenting or not metastasis. In addition, analysis of the correlation between the expression of ncRNAs and overall survival will be done using public databases of human melanoma samples. Taken together, this study might contribute to the establishment of novel strategies of prognosis, diagnosis and therapy for melanoma, and also to a better understanding of the role of ncRNAs in melanoma genesis and progression. (AU)