Regulation and impact of Argonaute 2 in melanoma

Argonautes是microRNAs的执行蛋白，这些小的非编码rna调节其他基因的表达。因此，Argonaute蛋白（AGOs）参与介导几乎所有重要的细胞过程，如增殖、凋亡、细胞周期调节和分化。黑色素瘤是十大最常见的实体肿瘤之一，在黑色素瘤的发展过程中，人类细胞中最丰富的AGO蛋白AGO2的蛋白表达减少。本项目的目的是确定这种黑色素瘤相关的AGO2下调的分子机制。根据我们的初步数据，这必须是一个转录后调控，最有可能由RNA结合蛋白（RBP）调节。在本研究中，我们计划确定这种RBP及其调控AGO2的具体机制。利用发现的RBP信息，我们将对细胞增殖、迁移、粘附独立生长和单细胞衍生生长进行广泛的研究，以深入了解恶性肿瘤细胞的各个层面的特性。这将使我们能够预测RBP的抑制和随后AGO2的重新表达是否会干扰黑色素瘤细胞的恶性特性，并可能对未来的治疗方法有用。

Argonautes are the executing proteins of microRNAs action, those small, non-coding RNAs regulating the expression of other genes. Thus, Argonaute proteins (AGOs) are involved in the mediation of almost all important cellular processes like proliferation, apoptosis, cell-cycle regulation, and differentiation. During development of melanoma, which is among the top ten of the most frequent solid types of tumors, protein expression of AGO2, the most abundant AGO protein in human cells, is diminished. The aim of this project is to identify the molecular mechanism of this melanoma-associated AGO2 downregulation. According to our preliminary data, it has to be a post-transcriptional regulation most likely modulated by an RNA binding protein (RBP). Within this study, we plan to identify this RBP and the specific mechanism regulating AGO2. Using the discovered information about the RBP, we will perform extensive studies about cell proliferation, migration, adhesion independent growth and single cell derived growth to gain insights into all levels of malignant tumor cell properties. This will allow us to predict if an inhibition of the RBP and subsequent re-expression of AGO2 interferes with malignant properties of melanoma cells and could be useful for future therapeutic approaches.