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Analysis of the function of miR-27b, miR-365 and miR-211 in progression and metastases of melanoma

Grant number: 18/23421-5
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): March 01, 2019
Effective date (End): June 30, 2019
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal Investigator:Miriam Galvonas Jasiulionis
Grantee:Enzo Reina Speciale
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Cutaneous Melanoma is the most lethal skin cancer among several types of skin cancers. It represents nearly 80 percent of cancer deaths and increasing constantly. Over the last decades, the number of registered cases has doubled (50.000 yearly deaths all over the world). The aggressiveness of the melanoma is due to its metastatic propensity grounded in parts on the aggressive melanoma cells invasion on the surrounding tissues, even when the primary tumor is significantly small in size. Some of the primary-tumor-melanoma-cells can invade the dermis, lymphatic vessels, append on the walls of distant organs and overflow inside the parenchyma, causing tiny metastatic issues still-to-be identified by newly techniques. These metastases grow progressively and develop in time, causing the patient's death. The malignant transformation of the common-acquired-nevus and the melanoma progression comprises a series of processes involving genetic and environmental factors. Among several molecular modifications in the process of the melanoma's progression, are amendments in the expression of micro-RNAs (mRNAs). Micro-RNAs regulate gene expression post-transcriptionally, for they can repress the translation or degrade messenger RNAs by inhibiting multiple different targets. By targeting so many targets, mRNAs affect diverse cellular processes such as cell proliferation, migration, invasion, angiogenesis, and resistance to apoptosis, and thus directly influence tumor Progression Some of the RNAs, as miR-27b, miR-365 e miR-211, have been described as presenting a regulatory role in some types of cancer, such as breast cancer, prostate cancer, lung adenocarcinoma, among others. However, its role in melanoma is still unknown. Using as a basis a linear-model of malignant transformation and progression of melanoma developed in our laboratory, this projects has in its objective to analyze the expression of miR-27b, miR-365 and miR-211 in the tumor lineage of this model, consisting in melanocytes, pre-malignant melanocytes (4C), non-metastatic (4C11-) and metastatic (4C11+) melanoma cells, to assess their importance in progression in metastatic melanoma. If the tumor is early-detected, prior to invading the dermis, surgical excision provides a cure in about 99% of patients. However, the 5-year survival rate drops to 15% and an average survival of 1 year for those with disseminated disease. The mRNAs identification specifically expressed in metastatic melanomas can be useful, not only to understand the melanoma biological composition but also as a biomarker of tumor aggressiveness.