MicroRNAs associated with the metastatic phenotype of melanoma

• Grant number: 13/04829-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2013
• End date: February 28, 2018
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Miriam Galvonas Jasiulionis
• Grantee: Ana Carolina Monteiro
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated scholarship(s): 16/09179-1 - The role of miRNA-298 in melanoma metastasis, BE.EP.DR

Abstract

Melanoma, tumor arising from melanocytes malignant transformation, is the most aggressive skin cancer. This tumor has elevated metastatic potencial and presents high resistance to treatments and, therefore, metastatic melanoma is currently considered an incurable disease. Among the molecules possibly involved in the genesis of this tumor are the microRNAs. MicroRNAs (miRNAs) are small molecules of about 22 nucleotides that regulate gene transcription by degradating target mRNA or by inhibiting protein translation. MiRNAs regulate approximately 30% of human mRNAs and are essential components of the control of several physiological processes, including cell proliferation, development and apoptosis. Recent studies indicate that miRNAs are involved in the progression of melanoma by targeting important mRNA pathways in this process, but little is known about how miRNAs are involved in the acquisition of metastatic phenotype by melanomas. Moreover, these molecules are promising tumor biomarkers. It was developed in our laboratory a murine model of melanocyte malignant transformation in which cell lines representing different phenotypes associated with melanoma were established after submitting the non-tumorigenic melanocyte lineage melan-a to sequential cycles of anchorage blockade. In this context, the main aims of this study are: identify pro-metastatic genes upregulated in the metastatic murine melanoma cell line 4C11+ relative to the non-metastatic murine melanoma cell line 4C11-; identify microRNAs targeting the mRNAs transcripts by these genes and having low expression in the 4C11+ cell line relative to the 4C11- lineage; ascertain the contribution of these miRNAs in the melanoma metastasis process. Besides better understanding the role of miRNAs in the metastatic phenotype of melanoma, this study may identify miRNAs as predictors of aggressiveness. (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)

MONTEIRO, ANA CAROLINA; MUENZNER, JULIENNE K.; ANDRADE, FERNANDO; RIUS, FLAVIA EICHEMBERGER; OSTALECKI, CHRISTIAN; GEPPERT, CAROL I.; AGAIMY, ABBAS; HARTMANN, ARNDT; FUJITA, ANDRE; SCHNEIDER-STOCK, REGINE; et al. Gene expression and promoter methylation of angiogenic and lymphangiogenic factors as prognostic markers in melanoma. MOLECULAR ONCOLOGY, v. 13, n. 6, p. 1433-1449, JUN 2019. (16/09179-1, 13/04829-0, 14/13663-0, 17/50122-6)