Regulation and impact of Argonaute 2 in melanoma

点击翻译按钮获取中文摘要

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.