Characterization of microRNA regulation and function in developmental and tumorigenic processes

microrna是一种短的非编码rna，广泛存在于真核生物中。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。在许多物种中，microrna与发育过程有关，最近还与肿瘤发生有关。该项目将重点关注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将在上皮细胞向间充质细胞（EMT）的转变过程中被表征，这在发育和转移中是重要的。EMT期间的表达差异已经确定。将对调控的microrna的靶基因、功能和对EMT信号通路的影响进行表征。由于EMT是转移的重要过程，我们将分析转移样本中microRNA的表达，并研究其对转移和侵袭的影响。在肾脏发育过程中，EMT过程被逆转，细胞经历间充质向上皮转化（MET）。因此，microRNA在肾脏发育和Wilms肿瘤发生中的功能将在该项目的第二部分进行表征。microrna的表达已经在肾母细胞瘤、胎儿和成人肾脏中得到了分析。对于至少十倍调控的microrna，靶基因、功能和信号通路将被确定。特别是，在Wilms肿瘤中过度表达的两个microrna将引起特别的兴趣，因为它们是由IGF2的内含子加工而成的，而IGF2是与Wilms肿瘤发生密切相关的基因。综上所述，这些研究将为阐明microrna在肿瘤发生、发展和转移中的作用做出有价值的贡献。

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.