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The role of miR-298 in the regulation of angiogenic factors in melanoma

Grant number: 19/14062-4
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): September 01, 2019
Effective date (End): August 31, 2020
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Miriam Galvonas Jasiulionis
Grantee:Mirella Yoko Kikuchi
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Cutaneous melanoma is a type of skin cancer that has its origin in the malignant transformation of melanocytes and although it has reduced prevalence compared to other types of neoplasms is the most aggressive type among skin tumors. Its aggressiveness is attributed mainly to its resistance to conventional therapies and its high metastatic capacity. One characteristic of this metastatic success is the formation of new blood vessels from pre-existing vessels, a process known as angiogenesis. This process can be related to several elements that include pro-angiogenic factors responsible for several pathways that act in this neovascularization until the regulation of small molecules such as microRNAs that are intrinsically related to the expression of these factors. Another mechanism capable of evidencing this melanoma aggressiveness due to the spread of cancer cells is vascular mimicry, where tumor cells express an endothelial cell phenotype, but these are absent in this type of development. Recent data obtained in our laboratory using a linear model of melanoma progression from murine melanocytes revealed that increased angiogenic factor angiopoietin 2 (Angpt2) expression and hypomethylation of its promoter and the Vegfc angiogenic factor promoter may be considered independent prognostic factors for the worse survival of patients with melanoma. In parallel, we identified in our model of melanoma study alteration in the expression of miR-298, which has among its predicted targets angiopoietin 2 and Vegfc. Thus, the purpose of this study is to elucidate the contribution of miR-298 to the regulation of angiogenic factors, such as Angpt2 and Vegfc, and the aggressiveness of melanoma. This study may contribute to a better understanding of the molecular mechanisms involved in the progression of melanoma and to the identification of new potential therapeutic targets.