Identifikation von miRNAs und ihrer Zielmoleküle mit Bedeutung für die chronische lymphatische Leukämie

MicroRNAs(MiRNAs)是最近被描述的一类内源性表达的短RNAs，它能在翻译阶段沉默基因的表达。它们参与了几乎所有多细胞生物体的发育过程，包括人类在内的所有能够实现短RNA基因沉默的多细胞生物体。此外，其中一些RNA的调节失调与不同的癌症有关。然而，miRNAs在正常和转化细胞生物学中的确切作用在很大程度上仍然难以捉摸。慢性淋巴细胞性白血病(CLL)是一种以多种不同染色体易位为特征的异质性白血病，其病因不明。两个miRNA基因在CLL中经常缺失，提示miRNAs参与了CLL的形成、进展或维持。识别miRNAs及其靶基因可能有助于深入了解慢性淋巴细胞性白血病的病因，并可能导致患者对治疗的反应。此外，对miRNA通路进行建模可以为未来的治疗应用识别病理相关的靶点。因此，本研究的具体目标是：1.鉴定CLL不同阶段的新miRNAs及其靶基因。2.CLL中miRNA与靶分子的相互作用和miRNA途径的特征。

MicroRNAs (miRNAs) constitute a recently described class of endogenously expressed short RNAs that silence gene expression at the translational step. They have been implicated in developmental processes in virtually all multicellular organisms capable of short RNA-directed gene silencing, including humans. In addition, dysregulation of some of these RNAs has been correlated with different cancers. The precise roles of miRNAs in the biology of normal and transformed cells, however, remain largely elusive. Chronic Lymphocytic Leukemia (CLL) is a heterogeneous leukemia characterized by several different chromosomal translocations whose etiology is unknown. Two miRNA genes are frequently deleted in CLL suggesting that miRNAs are involved in CLL formation, progress or maintenance. Identification of miRNAs and their target genes could lead to insights into CLL etiology and potentially a patient¿s response to therapy. In addition, modeling miRNA pathways could lead to identification of pathologically relevant targets for future therapeutic applications. Therefore, the specific aims of the proposed research project are: 1. Identification of novel miRNAs and their target genes in different stages of CLL. 2. Characterization of miRNA-target interactions and miRNA pathways in CLL.