Oertzenweg 19 b
14163 Berlin
+49 30 838 62225
biochemie@vetmed.fu-berlin.de
Only a few porcine microRNAs (miRNAs) are known. Because of their close phylogenetic distance to humans, pigs serve as a suitable model for studying intestinal development or disease. Recent studies indicate that miRNAs are key regulators of intestinal development and their aberrant expression leads to intestinal malignancy.
We have identified 205 novel miRNAs from porcine intestinal tissue after deep sequencing, miRDeep prediction [1] and microarray validation. Expression analysis along the entire intestine showed several functional clusters being partly loci specific. One of these clusters consists of eight miRNAs possessing increased expression in distal jejunum and ileum compared with other intestinal loci. Pathway analysis revealed these miRNAs to have a predominant impact on intracellular signalling pathways such as MAPK/ERK, Notch and Wnt signalling but also on Mets affected macrophage differentiation and p53 signaling pathway. Moreover, we were able to predict interactions between the mentioned miRNAs and the 3´ untranslated region (3´UTR) of potential targets by using the tool RNAhybrid [2], an algorithm that predicts multiple potential binding sites of miRNAs in large targets under calculation of a statistical significance of the binding site. Among others, all members of the trefoil peptide family (TFF1-3) were identified as potential targets of an identified miRNA possessing significantly calculated binding probabilities (pTFF1=0.017851, pTFF2=0.012536 and pTFF3=0.004350). TFFs are known as protective mucosal peptides mediating mucosal healing and restitution and are of particular interest in the developing intestine. Our ongoing research will evaluate the biological functionality of the predicted interactions based on reporter gene assays.