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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

iR-138-5p induces aggressive traits by targeting Trp53 expression in murine melanoma cells, and correlates with poor prognosis of melanoma patient

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da Cruz, Adriana Taveira [1] ; Hunger, Aline [2, 3] ; Machado de Melo, Fabiana Henriques [4, 1] ; Monteiro, Ana Carolina [1, 5] ; Pare, Genevieve Catherine [6] ; Lai, Dulce [6] ; Alves-Fernandes, Debora Kristina [1] ; Pedroso Ayub, Ana Luisa [1] ; Cordero, Esteban Mauricio [7] ; da Silveira Filho, Jose Franco [7] ; Schneider-Stock, Regine [5] ; Strauss, Bryan Eric [3] ; Tron, Victor [6, 7] ; Jasiulionis, Miriam Galvonas [1]
Total Authors: 14
[1] Univ Fed Sao Paulo, Dept Pharmacol, Escola Paulista Med, Sao Paulo, SP - Brazil
[2] Cristalia, Biotecnol Unidade 1, Rodoviaria SP 147, Itapira, SP - Brazil
[3] Univ Sao Paulo, Fac Med, Ctr Invest Translac Oncol LIM24, Inst Canc Estado Sao Paulo, Lab Vetores Virais, Sao Paulo, SP - Brazil
[4] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Sao Paulo, SP - Brazil
[5] Friedrich Alexander Univ, Dept Pathol, Erlangen, Bavaria - Germany
[6] Queens Univ, Dept Pathol & Mol Med, Kingston, ON - Canada
[7] Univ Fed Sao Paulo, Microbiol Immunol & Parasitol Dept, Sao Paulo, SP - Brazil
Total Affiliations: 7
Document type: Journal article
Source: Neoplasia; v. 23, n. 8, p. 823-834, AUG 2021.
Web of Science Citations: 0

Deregulation of miRNAs contributes to the development of distinct cancer types, including melanoma, an aggressive form of skin cancer characterized by high metastatic potential and poor prognosis. The expression of a set of 580 miRNAs was investigated in a model of murine melanoma progression, comprising non-metastatic (4C11-) and metastatic melanoma (4C11+) cells. A significant increase in miR-138-5p expression was found in the metastatic 4C11+ melanoma cells compared to 4C11-, which prompted us to investigate its role in melanoma aggressiveness. Functional assays, including anoikis resistance, colony formation, collective migration, serum-deprived growth capacity, as well as in vivo tumor growth and experimental metastasis were performed in 4C11- cells stably overexpressing miR-138-5p. miR-138-5p induced an aggressive phenotype in mouse melanoma cell lines leading to increased proliferation, migration and cell viability under stress conditions. Moreover, by overexpressing miR-138-5p, low-growing and non-metastatic 4C11- cells became highly proliferative and metastatic in vivo, similar to the metastatic 4C11+ cells. Luciferase reporter analysis identified the tumor suppressor Trp53 as a direct target of miR-138-5p. Using data sets from independent melanoma cohorts, miR-138-5p and P53 expression were also found deregulated in human melanoma samples, with their levels negatively and positively correlated with prognosis, respectively. Our data shows that the overexpression of miR-138-5p contributes to melanoma metastasis through the direct suppression of Trp53. (AU)

FAPESP's process: 12/08776-5 - MicroRNAs involved in melanoma genesis and progression
Grantee:Miriam Galvonas Jasiulionis
Support Opportunities: Regular Research Grants
FAPESP's process: 18/20775-0 - Non-coding RNAs involved with melanoma genesis and progression
Grantee:Miriam Galvonas Jasiulionis
Support Opportunities: Regular Research Grants
FAPESP's process: 10/18484-6 - Identification of miRNA involved with melanoma genesis and epigenetic regulation of their expression
Grantee:Adriana Taveira da Cruz
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 14/13663-0 - Integrating gene and microRNA expression, methylome and hidroxymethylome data from different phases of melanoma progression.
Grantee:Miriam Galvonas Jasiulionis
Support Opportunities: Regular Research Grants