miRNAs in malignant melanoma progression
âI am interested in miRNAs. I was able to associate miRNA targets with processes that can promote metastagenesis in malignant melanoma.â
MicroRNAs are ~21nt long molecules that have been found to regulate translation of target mRNAs in many cellular processes; tissue specific and in response to environmental changes. Malignant melanoma progression is one example for metastasis development that goes in hand with a characteristic expression profile of the miRNAome.
The question we focused on is: Which miRNAs are involved in the regulation of malignant melanoma progression and what are the key targets and their function?
It is particularly interesting to detect the mechanism how microRNAs choose their targets and what is the induced change in a particular cellular system. By answering these urgent questions the understanding of an entire cell regulatory machinery is at hand and previously unexpected cell physiological phenomena might become explainable.
We performed miRNA expression screens using qRT-PCR in samples of different disease states from melanoma patients. We examined state-of-the-art target prediction algorithms and finally selected high confidence predictions from their prediction intersection. Subsequently, we performed gene annotation enrichment analysis for GO terms, pathways and diseases.
A set of 14 miRNAs has been identified as significantly differentially expressed in metastasis vs. primary melanoma. Highly regulated target genes are tumour suppressors like PTEN. Targets released from miRNA induced repression are e.g. cell cycle regulators wee1 and CDKN1A. Further, an enrichment in translation regulation by melanoma metastamir where observed for pathways like apoptosis, MAPK signalling, proliferation, focal adhesion and angiogenesis.
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German Conference on Bioinformatics, Potsdam (Germany), 26 September - 28 September 2007
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