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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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Author(s):
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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
Affiliation:
[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
Abstract

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 type: Regular Research Grants
FAPESP's process: 18/20775-0 - Non-coding RNAs involved with melanoma genesis and progression
Grantee:Miriam Galvonas Jasiulionis
Support type: 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 type: 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 type: Regular Research Grants