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

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.