Melanoma is a highly invasive malignant skin tumor having high metastatic rate and poor prognosis. The biology of melanoma is controled by miRNAs. The miRNA-183 cluster, which is composed of miRNA-183∼96∼182 genes, plays an important roles in tumor development. In order to investigate the role and action of miRNA-183 cluster in B16 cells, we overexpressed and knocked down miRNA-183 cluster in B16 cells. Using bioinformatics analysis, we predicted that the key framscript factor of melangenic genes. Microphthalmia-associated transcription factor (MITF) is one of the targets of miRNA-183 cluster. The results of Luciferase activity assays confirmed that MITF was targeted by miRNA-183 cluster. Overexpression and knockdown of miRNA-183 cluster in B16 cells resulted in down and up regulation of MITF expression, respectively at both mRNA and protein levels. Furthmore, overexpression and knockdown of the miRNA-183 cluster in B16 cells decreased and increased the expression of mRNA and protein of melangenic genes tyrosinase (TYR), and tyrosinase-related protein 1 (TYRP1), dopachrome-tautomerase (DCT), as well as the production of melanins and eumelanin production, respectively. On the proliferation and migration pathway, overexpression and knockdown of miRNA-183 cluster increased and decreased, respectively the expression of mRNA and protein of mitogen-activated protein kinase 1 (MEK1), extracellular regulated protein kinases1/2 (ERK1/2) and cAMP-responsive-element binding protein (CREB). These results indicated that miRNA-183 cluster regulated melanogenesis in B16 cells as well as cell proliferation and migration by directly targeting MITF through migration pathway.

中文翻译：

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miRNA-183〜96〜182调节B16细胞的黑色素生成，细胞增殖和迁移。

黑色素瘤是具有高转移率和不良预后的高侵袭性恶性皮肤肿瘤。黑色素瘤的生物学受miRNA控制。由miRNA-183〜96〜182基因组成的miRNA-183簇在肿瘤的发展中起着重要作用。为了研究miRNA-183簇在B16细胞中的作用和作用，我们过表达并敲低了B16细胞中的miRNA-183簇。使用生物信息学分析，我们预测了黑色素基因的关键框架因子。小眼症相关转录因子（MITF）是miRNA-183簇的目标之一。萤光素酶活性测定的结果证实MITF被miRNA-183簇靶向。B16细胞中miRNA-183簇的过度表达和敲低导致MITF表达的上下调节，分别在mRNA和蛋白质水平上。此外，B16细胞中miRNA-183簇的过表达和敲低降低并增加了黑色素基因酪氨酸酶（TYR）和酪氨酸酶相关蛋白1（TYRP1），多巴色素-互变异构酶（DCT）的mRNA和蛋白的表达。作为黑色素的生产和黑色素的生产。在增殖和迁移途径中，miRNA-183簇的过表达和敲低分别增加和减少，分别是有丝分裂原激活蛋白激酶1（MEK1），细胞外调节蛋白激酶1/2（ERK1 / 2）和cAMP的mRNA和蛋白表达。反应元件结合蛋白（CREB）。