Characterization of microRNA regulation and function in developmental and tumorigenic processes

发育和致瘤过程中 microRNA 调控和功能的表征

• 批准号: 27829949
• 负责人: Professor Dr. Sven Diederichs
• 金额: --
• 依托单位: Mass General Cancer Center
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2006
• 资助国家: 德国
• 起止时间: 2005-12-31 至 2007-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/27829949?language=en
• 关键词: Characterization; microRNA; regulation; function; developmental

MicroRNAs are short, non-coding RNAs identified in a broad range of eukaryotes. They regulate gene expression by targeting coding mRNAs for cleavage or translational blockage. In a variety of species, microRNAs have been linked to developmental processes and have recently been implicated in tumorigenesis. The proposed project will focus on the role of microRNAs in epithelial plasticity and thus contribute to our understanding of microRNA function in development, tumorigenesis and tumor progression. First, microRNAs will be characterized at the transition from epithelial to mesenchymal cells (EMT), which is important in development and metastasis. Expression differences during EMT have already been determined. Target genes, function and effects on EMT signaling pathways of the regulated microRNAs will be characterized. Since EMT is an essential process in metastasis, microRNA expression will be analyzed in metastasis samples and their effect on migration and invasion will be studied. During kidney development, the process of EMT is reversed and cells undergo mesenchymal to epithelial transition (MET). Therefore, microRNA function will be characterized in kidney development and Wilms tumorigenesis in the second part of the project. Expression of microRNAs has already been profiled in Wilms tumors, fetal and adult kidney. For microRNAs at least tenfold regulated, target genes, function and signaling pathways will be identified. Particularly, two microRNAs overexpressed in Wilms tumors will be of special interest since they are processed from an intron of IGF2 - a gene that is intimately linked to Wilms tumorigenesis. In summary, these studies shall make a valuable contribution to elucidate the role of microRNAs in development, tumorigenesis and metastasis.

MicroRNA 是在多种真核生物中发现的短的非编码 RNA。它们通过靶向编码 mRNA 进行切割或翻译阻断来调节基因表达。在多种物种中，microRNA 与发育过程有关，并且最近被认为与肿瘤发生有关。拟议的项目将重点关注 microRNA 在上皮可塑性中的作用，从而有助于我们了解 microRNA 在发育、肿瘤发生和肿瘤进展中的功能。首先，microRNA 将在从上皮细胞向间充质细胞 (EMT) 的转变过程中进行表征，这对于发育和转移很重要。 EMT 期间的表达差异已经确定。将表征受调节的 microRNA 的靶基因、功能和对 EMT 信号通路的影响。由于EMT是转移中的一个重要过程，因此将分析转移样本中的microRNA表达，并研究它们对迁移和侵袭的影响。在肾脏发育过程中，EMT 过程发生逆转，细胞经历间充质到上皮细胞的转变 (MET)。因此，在该项目的第二部分中，microRNA 的功能将在肾脏发育和肾母细胞瘤发生中得到表征。 microRNA 的表达已经在肾母细胞瘤、胎儿和成人肾脏中进行了分析。对于至少受到十倍调控的 microRNA，将确定靶基因、功能和信号通路。特别是，在肾母细胞瘤中过度表达的两种 microRNA 将受到特别关注，因为它们是由 IGF2 的内含子加工而成的，IGF2 是与肾母细胞瘤发生密切相关的基因。总之，这些研究将为阐明 microRNA 在发育、肿瘤发生和转移中的作用做出有价值的贡献。