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

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

doi:10.18632/oncotarget.21774

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.

Highlights

MicroRNAs are short (~22nt) non-coding RNAs that are widely implicated in translational repression and degradation of target mRNAs, and estimated to downregulate up to 60% of genes [1]
We used 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
Cellular and circulating miRNAs have been linked to colorectal cancer (CRC), a common and severe form of cancer that often arises from adenomas in the colon and rectum [3, 4]

Summary

Introduction

MicroRNAs are short (~22nt) non-coding RNAs that are widely implicated in translational repression and degradation of target mRNAs, and estimated to downregulate up to 60% of genes [1]. They are emerging as predictive and prognostic biomarkers and as therapeutic targets in a wide range of human diseases, including cancer [2]. Colorectal cancer is the third most commonly diagnosed cancer in males, second in females, and estimated to cause more than 600,000 deaths per year worldwide [5]. Development of strategies to prevent, diagnose and treat CRC will be aided by animals that model the disease and predict efficacy in humans

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