Peroxiredoxin-2 represses NRAS-mutated melanoma cells invasion by modulating EMT markers

Author(s)

Noma, Isabella Harumi Yonehara ; Carvalho, Larissa Anastacio da Costa ; Camarena, Denisse Esther Mallaupoma ; Silva, Renaira Oliveira ; de Moraes, Manoel Oliveira ; de Souza, Sophia Tavares ; Newton-Bishop, Julia ; Nsengimana, Jeremie ; Maria-Engler, Silvya Stuchi

• Document type: Journal article
• Source: BIOMEDICINE & PHARMACOTHERAPY; v. 177, p. 13-pg., 2024-07-01.

Abstract

The second most common mutation in melanoma occurs in NRAS oncogene, being a more aggressive disease that has no effective approved treatment. Besides, cellular plasticity limits better outcomes of the advanced and therapy -resistant patients. Peroxiredoxins (PRDXs) control cellular processes through direct hydrogen peroxide oxidation or by redox-relaying processes. Here, we demonstrated that PRDX2 could act as a modulator of multiple EMT markers in NRAS-mutated melanomas. PRDX2 knockdown lead to phenotypic changes towards invasion in human reconstructed skin and the treatment with a PRDX mimetic (gliotoxin), decreased migration in PRDX2-deficient cells. We also confirmed the favorable clinical outcome of patients expressing PRDX2 in a large primary melanoma cohort. This study contributes to our knowledge about genes involved in phenotype switching and opens a new perspective for PRDX2 as a biomarker and target in NRAS-mutated melanomas. (AU)

• FAPESP's process: 22/09245-5 - Metastatic potential of peroxyredoxin 2 in NRAs-mutated Melanomas
• Grantee: Silvya Stuchi Maria-Engler
• Support Opportunities: Regular Research Grants
• FAPESP's process: 22/08041-7 - Evaluation of the effect of conoidin A on the proliferative and invasive potential of NRAS mutant melanoma cells
• Grantee: Sophia Tavares de Souza
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 20/14019-9 - Potential of orange oil and neem oil in the control of coffee leaf miner Leucoptera coffeella (Lepidoptera: Lyonetiidae) and selectivity to the predator Chrysoperla externa (Neuroptera: Chrysopidae)
• Grantee: Vinicius de Oliveira Lima
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 17/04926-6 - Melanoma and chemoresistance: in vitro and in silico models to exploit therapeutic targets
• Grantee: Silvya Stuchi Maria-Engler
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/14936-1 - Mitochondrial metabolism dictates the heterogeneity and resistance of melanoma
• Grantee: Larissa Anastacio da Costa Carvalho
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 20/15042-4 - Antiproliferative and cell invasion inhibitor potencial of new copper (II) complexes in human Melanoma with resistance to BRAF inhibitors phenotype
• Grantee: Manoel Oliveira de Moraes Junior
• Support Opportunities: Scholarships in Brazil - Doctorate