miR-138-5p induces aggressive traits by targeting Trp53 expression in murine melanoma cells, and correlates with poor prognosis of melanoma patients
| Autor: | Esteban Mauricio Cordero, Ana Luisa Pedroso Ayub, Ana Carolina Monteiro, Bryan E. Strauss, Miriam Galvonas Jasiulionis, Adriana Taveira da Cruz, Fabiana Henriques Machado de Melo, Victor Tron, Aline Hunger, Dulce Lai, Débora Kristina Alves-Fernandes, Regine Schneider-Stock, Geneviève C. Paré, José Franco da Silveira Filho |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
miR-138-5p Trp53 Biology Metastasis Mice Aggressiveness Cell Line Tumor microRNA medicine Animals Humans Viability assay miR-138 Neoplasm Metastasis 3' Untranslated Regions Melanoma RC254-282 Original Research Neoplasm Staging Cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Prognosis Survival Analysis Gene Expression Regulation Neoplastic MicroRNAs Cell culture Cancer research RNA Interference Skin cancer Tumor Suppressor Protein p53 |
| Zdroj: | Neoplasia: An International Journal for Oncology Research, Vol 23, Iss 8, Pp 823-834 (2021) Neoplasia (New York, N.Y.) |
| ISSN: | 1476-5586 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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