Altered microRNA profiles during early colon adenoma progression in a porcine model of familial adenomatous polyposis
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Monika Stachowiak1, Tatiana Flisikowska2, Stefan Bauersachs3,4, Carolin Perleberg2, Hubert Pausch5, Marek Switonski1, Alexander Kind2, Dieter Saur6, Angelika Schnieke2 and Krzysztof Flisikowski2
1Department of Genetics and Animal Breeding, Poznan University of Life Sciences, 60-637 Poznan, Poland
2Chair of Livestock Biotechnology, Technische Universität München, 85354 Freising, Germany
3Institute of Agricultural Sciences, Animal Physiology, ETH Zurich, CH-8092 Zurich, Switzerland
4Current address: University of Zurich, Clinic for Animal Reproduction Medicine, Genetics and Functional Genomics Group, CH-8092 Zurich, Switzerland
5Institute of Agricultural Sciences, Animal Genomics, ETH Zurich, CH-8092 Zurich, Switzerland
6Klinikum Rechts der Isar II, Technische Universität München, 81675 Munich, Germany
Krzysztof Flisikowski, email: [email protected]
Keywords: colorectal cancer; dysplasia; isomiR; microRNA; pig model
Received: August 02, 2017 Accepted: September 23, 2017 Published: October 10, 2017
MicroRNAs are dysregulated in various cancers including colorectal cancer, and are potential useful biomarkers of disease development. We used next generation sequencing to investigate miRNA expression profiles in low- and high-grade intraepithelial dysplastic polyps from pigs carrying a mutation in the adenomatous polyposis coli tumour suppressor (APC1311, orthologous to human APC1309) that model an inherited predisposition to colorectal cancer, familial adenomatous polyposis. We identified several miRNAs and their isomiRs significantly (P < 0.05) differentially expressed between low and high-grade intraepithelial dysplastic polyps. Of these, ssc-let-7e, ssc-miR-98, ssc-miR-146a-5p, ssc-miR-146b, ssc-miR-183 and ssc-miR-196a were expressed at higher level and ssc-miR-126-3p at lower level in high-grade intraepithelial dysplastic polyps. Functional miRNA target analysis revealed significant (P < 0.001) over-representation of cancer-related pathways, including ‘microRNAs in cancer’, ‘proteoglycans in cancer’, ’pathways in cancer’ and ‘colorectal cancer’. This is the first study to reveal miRNAs associated with premalignant transformation of colon polyps.
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