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.

miRNA 的失调导致不同癌症类型的发展，包括黑色素瘤，这是一种侵袭性皮肤癌，其特征是高转移潜能和不良预后。在小鼠黑色素瘤进展模型中研究了一组 580 个 miRNA 的表达，包括非转移性 (4C11-) 和转移性黑色素瘤 (4C11+) 细胞。与 4C11- 相比，在转移性 4C11+ 黑色素瘤细胞中发现 miR-138-5p 表达显着增加，这促使我们研究其在黑色素瘤侵袭性中的作用。功能测定，包括失巢凋亡抗性、菌落形成、集体迁移、血清剥夺生长能力以及体内在稳定过表达 miR-138-5p 的 4C11 细胞中进行肿瘤生长和实验性转移。miR-138-5p 在小鼠黑色素瘤细胞系中诱导侵袭性表型，导致应激条件下增殖、迁移和细胞活力增加。此外，通过过表达 miR-138-5p，低生长和非转移性 4C11- 细胞在体内变得高度增殖和转移，类似于转移性 4C11+ 细胞。荧光素酶报告基因分析确定了肿瘤抑制因子Trp53作为 miR-138-5p 的直接靶标。使用来自独立黑色素瘤队列的数据集，在人类黑色素瘤样本中也发现 miR-138-5p 和 P53 表达失调，它们的水平分别与预后呈负相关和正相关。我们的数据表明，miR-138-5p 的过表达通过直接抑制Trp53促进黑色素瘤转移。