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Identification of miRNAs with a role in regulating of phenotype switching in melanoma

Grant number: 23/01959-1
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): June 01, 2023
Effective date (End): May 31, 2024
Field of knowledge:Biological Sciences - Biology
Principal Investigator:Miriam Galvonas Jasiulionis
Grantee:Camila Farias
Host Institution: Instituto Nacional de Farmacologia (INFAR). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Melanoma is the most aggressive type of skin cancer due to its ability to generate metastases. It arises from the malignant transformation of melanocytes, the cells responsible for producing melanin, the pigment that gives the skin, eyes, and hair their color. Prolonged exposure to UV light is one of the main factors contributing to the development of melanoma. This aggressiveness and invasiveness of other tissues occurs, among other factors, due to cellular plasticity, that is, the ability of cells to change their phenotype in response to adaptation to the microenvironment. In melanoma, cells transition from a highly proliferative and differentiated phenotype to a less proliferative, invasive, and undifferentiated phenotype. Cellular plasticity allows cells to transit between different transcriptional and phenotypic states without necessarily undergoing genetic changes. Epigenetics has demonstrated an important role in regulating phenotype change. Studies have already shown that post-translational modifications of histones and microRNAs can suppress the transcription of adhesion proteins such as E-cadherin. MicroRNAs are small non-coding RNAs that act by promoting the inhibition of target mRNA translation. In melanoma, miRNAs regulate proliferation, cell migration, and metastasis formation by acting on essential transcription factors in these pathways. For example, miR-148 binds to the MITF (microphthalmia associated transcription factor) RNA, reducing its expression, interfering with the cell cycle of melanocytes. Our laboratory has mouse melanocyte cell lines that allow us to study cellular plasticity. Among the melanoma cell lines, we have those that present both the less proliferative and undifferentiated phenotype (4C and 4C11-) and the highly proliferative and differentiated phenotype (4C11+), as described in human melanoma cells. We analyzed the expression of more than 300 miRNAs in these cell lines and based on this profile selected the microRNAs miR-138/2-5p, which showed high expression in the 4C11+ line, and miR-125-5p, which has high expression in the 4C11-, to study their relationship with cellular plasticity in melanoma.Keywords: Melanoma, cell plasticity, EMT, microRNAs.

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