Analysis of miRNAs as Tumor-Initiators

MicroRNAs (miRNAs) belong to a new class of small, non-coding RNA molecules, which regulate the expression of protein-coding genes by a mechanism known as RNA interference (RNAi). They are transcribed as part of polycistronic RNA-molecules (pri-miRNAs) and are processed in the nucleus via Drosha leading to precursor-miRNAs (pre-miRNA; 70-100 nucleotides). These pre-miRNAs are exported into the cytoplasm by exportin-5, procesed to mature miRNAs (19-23 nucleotides), and bound by the miRNP-complex. This complex is strongly related to the RISC-complex (RNA-Induced Silencing Complex), the central mediator of the RNAi-mechnism. In contrast to the small-interfering RNAs (siRNAs), which bind their mRNA targets with perfect complementarity, most miRNAs bind to their targets with near perfect complementarity mediating translational repression instead of mRNA degradation. A couple of cell-type specific mammalian miRNAs are identified, which are involved in regulation of cellular processes like differentiation, proliferation, migration, stress response, apoptosis and haematopoiesis, therefore miRNAs may exhibit a high impact for carcinogenesis. Moreover, a number of recent studies reported altered expression of specific miRNAs and their target genes, contributing to the initiation and progression of cancer. To understand the biological function of miRNAs, it is important to identify their targets.