The suppressive activity of monocyte chemoattractant protein 1‐induced protein 1 (MCPIP1) an inflammation‐related ribonuclease, has been described in a few cancer types but has yet to be assessed in the most common subtype of skin cancer: melanoma. Here, we have evaluated the MCPIP1 expression in melanoma tissues by reanalysis of publicly available transcriptome data from 89 melanoma samples, and immunohistochemical staining of 21 primary and 81 metastatic melanomas. Our data implicated decreased MCPIP1 expression in melanoma tumors compared to normal tissues, and positive correlation between high ribonuclease expression and melanoma‐specific survival of patients. To investigate the ribonuclease activity in melanoma cells, MCPIP1 was ectopically expressed in the MV3 human melanoma cell line. Following the transcriptome, proteome, and intracellular signaling of MCPIP1‐overexpressing MV3 cells was assessed via real‐time quantitative polymerase chain reaction, Western blot analysis, and RNAseq. MV3 cells overexpressing MCPIP1 exhibited a broad range of alterations in the transcriptome and proteome, as well as in the phosphorylation status of a number of proteins, strongly indicating MCPIP1‐dependent cell cycle arrest and inhibition of Akt/mTOR signaling in these cells. Moreover, we have shown, that MCPIP1 overexpression downregulates miRNA‐193a‐3p expression in MV3 cells. Furthermore, the majority of the described effects were dependent on the ribonucleolytic activity of the protein. The presented body of data strongly suggests a potential tumor suppressor role and possible future application as a positive prognostic marker of MCPIP1 protein in melanoma.

中文翻译：

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MCPIP1表达与患者黑素瘤特异性存活呈正相关，其过表达影响人类黑素瘤细胞的重要细胞内途径

单核细胞趋化蛋白1诱导蛋白1（MCPIP1）是一种与炎症相关的核糖核酸酶的抑制活性，已在几种癌症类型中进行了描述，但尚未在皮肤癌的最常见亚型中进行评估：黑色素瘤。在这里，我们通过重新分析来自89个黑色素瘤样品的公开转录组数据以及21个原发性和81个转移性黑色素瘤的免疫组化染色，评估了黑色素瘤组织中MCPIP1的表达。我们的数据表明与正常组织相比，黑色素瘤肿瘤中MCPIP1表达降低，并且核糖核酸酶高表达与患者黑色素瘤特异性存活之间呈正相关。为了研究黑色素瘤细胞中的核糖核酸酶活性，MCPIP1在MV3人黑色素瘤细胞系中异位表达。在转录组，蛋白质组之后，通过实时定量聚合酶链反应，蛋白质印迹分析和RNAseq对MCPIP1过表达MV3细胞的细胞内信号传导进行了评估。过量表达MCPIP1的MV3细胞在转录组和蛋白质组以及许多蛋白质的磷酸化状态方面表现出广泛的变化，强烈表明MCPIP1依赖的细胞周期停滞并抑制了这些细胞中的Akt / mTOR信号传导。此外，我们已经表明，MCPIP1过表达下调了MV3细胞中的miRNA‐193a‐3p表达。此外，所描述的大多数作用取决于蛋白质的核糖核酸分解活性。本文提供的大量数据强烈暗示了潜在的抑癌作用，并可能作为MCPIP1蛋白在黑色素瘤中的预后指标。