MicroRNA-5p and -3p co-expression and cross-targeting in colon cancer cells

Background: two mature mirna species may be generated from the 5' and 3' arms of a pre-mirna precursor. in most cases,only one species remains while the complementary species is degraded. however,co-existence of mirna-5p and -3p species is increasingly being reported. in this work,we aimed to systematically investigate co-expression of mirna-5p/3p in colon cancer cells in a genome-wide analysis,and to examine cross-targeting of the dysregulated mirnas and 5p/3p species.results: four colon cancer cell lines were examined relative to two normal colon tissues. of the 1,190 mirnas analyzed,92 and 36 were found to be up- or down-regulated,respectively,in cancer cells. nineteen co-expressed mirna-5p/3p pairs were further identified suggesting frequent 5p/3p co-accumulation in colon cancer cells. of these,14 pairs were co-up-regulated and 3 pairs were co-down-regulated indicating concerted 5p/3p dysregulation. nine dysregulated mirna pairs fell into three mirna gene families,namely let-7,mir-8/200 and mir-17,which showed frequent cross-targeting in the metastasis process. focusing on the let-7d-5p/3p pair,the respectively targeted igf1r and kras were shown to be in a reverse relationship with expression of the respective mirna,which was confirmed in transient transfection assays using let-7d mimic or inhibitor. targeting of kras by let-7d was previous reported; targeting of igf1r by let-7d-5p was confirmed in luciferase assays in this study. the findings of let-7d-5p/3p and multiple other mirnas targeting igf1r,kras and other metastasis-related factors suggest that 5p/3p mirnas contribute to cross-targeting of multiple cancer-associated factors and processes possibly to evade functional abolishment when any one of the crucial factors are inactivated.conclusions: mirna-5p/3p species are frequently co-expressed and are coordinately regulated in colon cancer cells. in cancer cells,multiple cross-targeting by the mirnas,including the co-existing 5p/3p species,frequently occurs in an apparent safe-proof scheme of mirna regulation of important tumorigenesis processes. further systematic analysis of co-existing mirna-5p/3p pairs in clinical tissues is important in elucidating 5p/3p contributions to cancer pathogenesis. © 2014 choo et al.; licensee biomed central ltd.