Regulation and impact of Argonaute 2 in melanoma

Argonaute 2 对黑色素瘤的调控和影响

• 批准号: 465381242
• 负责人: Professorin Dr. Anja-Katrin Bosserhoff
• 金额: --
• 依托单位: Lehrstuhl für Biochemie und Molekulare Medizin
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/465381242?language=en
• 关键词: Regulation; impact; Argonaute; melanoma

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.

Argonautes 是 microRNA 作用的执行蛋白，这些小非编码 RNA 调节其他基因的表达。因此，Argonaute 蛋白 (AGO) 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。黑色素瘤是最常见的十种实体肿瘤之一，在黑色素瘤的发展过程中，人类细胞中最丰富的 AGO 蛋白 AGO2 的蛋白表达减弱。该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，它很可能是由 RNA 结合蛋白 (RBP) 调节的转录后调控。在这项研究中，我们计划确定该 RBP 和调节 AGO2 的具体机制。利用已发现的有关 RBP 的信息，我们将进行有关细胞增殖、迁移、粘附独立生长和单细胞衍生生长的广泛研究，以深入了解恶性肿瘤细胞的各个级别的特性。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，并且可能对未来的治疗方法有用。