Department of Pharmacy, University of Pisa, 56126 Pisa, Italy.
Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, 56128 Pisa, Italy.
Int J Mol Sci. 2020 Aug 27;21(17):6183. doi: 10.3390/ijms21176183.
Remarkable deregulation of several microRNAs (miRNAs) is demonstrated in cutaneous melanoma. hsa-miR-193a-3p is reported to be under-expressed in tissues and in plasma of melanoma patients, but the role of both miR-193a arms in melanoma is not known yet.
After observing the reduced levels of miR-193a arms in plasma exosomes of melanoma patients, the effects of hsa-miR-193a-3p and -5p transfection in cutaneous melanoma cell lines are investigated.
In melanoma cell lines A375, 501Mel, and MeWo, the ectopic over-expression of miR-193a arms significantly reduced cell viability as well as the expression of genes involved in proliferation (ERBB2, KRAS, PIK3R3, and MTOR) and apoptosis (MCL1 and NUSAP1). These functional features were accompanied by a significant downregulation of Akt and Erk pathways and a strong increase in the apoptotic process. Since in silico databases revealed TROY, an orphan member of the tumor necrosis receptor family, as a potential direct target of miR-193a-5p, this possibility was investigated using the luciferase assay and excluded by our results.
Our results underline a relevant role of miR-193a, both -3p and -5p, as tumor suppressors clarifying the intracellular mechanisms involved and suggesting that their ectopic over-expression could represent a novel treatment for cutaneous melanoma patients.
在皮肤黑色素瘤中，几个 microRNAs（miRNAs）的表达出现显著失调。据报道，hsa-miR-193a-3p 在组织和黑色素瘤患者的血浆中表达下调，但 miR-193a 两个臂在黑色素瘤中的作用尚不清楚。
在观察到黑色素瘤患者血浆外泌体中 miR-193a 臂水平降低后，研究了 hsa-miR-193a-3p 和 -5p 转染对皮肤黑色素瘤细胞系的影响。
在黑色素瘤细胞系 A375、501Mel 和 MeWo 中，miR-193a 臂的异位过表达显著降低了细胞活力以及参与增殖（ERBB2、KRAS、PIK3R3 和 MTOR）和凋亡（MCL1 和 NUSAP1）的基因表达。这些功能特征伴随着 Akt 和 Erk 通路的显著下调和凋亡过程的强烈增加。由于在计算机数据库中发现 TROY，一种肿瘤坏死受体家族的孤儿成员，是 miR-193a-5p 的潜在直接靶标，因此使用荧光素酶测定法研究了这种可能性，但我们的结果排除了这种可能性。
我们的结果强调了 miR-193a（包括 -3p 和 -5p）作为肿瘤抑制因子的重要作用，阐明了涉及的细胞内机制，并表明其异位过表达可能代表一种新的治疗皮肤黑色素瘤患者的方法。
