Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São Paulo, Avenida Professor Lineu Prestes, 580, São Paulo, SP 05508-00, Brazil.
Leeds Institute of Medical Research, School of Medicine, University of Leeds, Leeds LS9 7TF, UK.
Biomed Pharmacother. 2024 Aug;177:116953. doi: 10.1016/j.biopha.2024.116953. Epub 2024 Jul 1.
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.
黑色素瘤中第二常见的突变发生在 NRAS 癌基因中，这种疾病更具侵袭性，目前尚无有效的批准治疗方法。此外，细胞可塑性限制了晚期和耐药患者的更好治疗效果。过氧化物还原酶（PRDXs）通过直接过氧化氢氧化或通过氧化还原传递过程来控制细胞过程。在这里，我们证明 PRDX2 可以作为 NRAS 突变黑色素瘤中多种 EMT 标志物的调节剂。PRDX2 敲低导致人重建皮肤中向侵袭表型的变化，而 PRDX 模拟物（gliotoxin）的治疗减少了 PRDX2 缺陷细胞的迁移。我们还在一个大型原发性黑色素瘤队列中证实了表达 PRDX2 的患者的良好临床结果。这项研究有助于我们了解参与表型转换的基因，并为 PRDX2 作为 NRAS 突变黑色素瘤的生物标志物和靶点开辟了新的视角。
Biomed Pharmacother. 2024-8
Melanoma Res. 2019-6
J Invest Dermatol. 2016-2
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