Oncotarget

Research Papers:

Altered microRNA profiles during early colon adenoma progression in a porcine model of familial adenomatous polyposis

Monika Stachowiak, Tatiana Flisikowska, Stefan Bauersachs, Carolin Perleberg, Hubert Pausch, Marek Switonski, Alexander Kind, Dieter Saur, Angelika Schnieke and Krzysztof Flisikowski _

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Oncotarget. 2017; 8:96154-96160. https://doi.org/10.18632/oncotarget.21774

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Abstract

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

Correspondence to:

Krzysztof Flisikowski, email: flisikowski@wzw.tum.de

Keywords: colorectal cancer; dysplasia; isomiR; microRNA; pig model

Received: August 02, 2017    Accepted: September 23, 2017    Published: October 10, 2017

ABSTRACT

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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