PO-350 MiRNAs and their relation to biological pathways in left- and right-sided colorectal cancer

Abstract

IntroductionMicroRNAs (miRNAs) are involved in the regulation of gene expression in colorectal cancer (CRC), which has specific biological pathways that are predominant in either left- or right-sided CRC. However, it is unclear how miRNAs are associated with biological pathways in these two forms of CRC. Our hypothesis is that a comprehensive understanding of the fundamental biological signalling pathways in the two sides of CRC may aid in developing a decisive step towards precision medicine. We aim to clarify specific biological pathway differences of differentially expressed miRNAs between left- and right-sided CRC.Material and methodsWe extracted total RNA from 24 of left- and right-sided CRC tumour samples from Finnish patients using the mirVanaTM miRNA Isolation Kit (Thermo Fisher Scientific) in the discovery cohort. Libraries for small RNA sequencing were prepared using TruSeq® Small RNA Library Prep Kit (Illumina) and run on Illumina MiSeq. Differentially up-regulated miRNAs were identified using DeSeq2. For validation purposes, we used the mature miRSeq dataset of 201 CRC samples from The Cancer Genome Atlas. We analysed biological pathways of site-specific miRNAs from the discovery and validation cohorts using the DIANA/mirPath tool.Results and discussionsWe found 17 and 15 differentially up-regulated miRNAs in left- and right-sided CRC, respectively, in the discovery cohort. The left miRNAs were involved in the mTor, Wnt, PI3K-Akt signalling pathways. These pathways are the predominant pathways in left-sided CRC. The Wnt signalling pathway was also significant (false discovery rate <0.05) in the left miRNAs from the validation cohort. In the discovery cohort, the right miRNAs were involved in the TGF-β signalling pathway. This pathway is dominant in right-sided CRC also in earlier reports. Alongside with the pathway findings, we found that the discovery and validation cohorts share six miRNAs. One of these (hsa-miR-196b-5p) was differentially up-regulated in left-sided CRC and the rest of them (hsa-miR-625–3 p, hsa-miR-155–5 p, hsa-miR-625–5 p, hsa-miR-31–5 p and hsa-miR-330–5 p) in right-sided CRC.ConclusionOur findings highlight that there are site-specific miRNAs in left and right-sided CRC. The results also indicate the involvement of these left and right miRNAs in different predominant biological pathways of the two forms of CRC. This exploration may be useful for further studies on the development of diagnosis in left- and right-sided CRC.