| Resumo: | Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and a frequent cause of cancer related deaths worldwide. Despite recent advances, CRC characterization still exhibits a lot to unveil, especially regarding the epigenetic contribution of miRNAs on disease initiation and progression. MicroRNAs (miRNAs) are a class of small (21-23 nucleotides) endogenous non-coding RNAs that regulate gene expression at a post-transcriptional level. MiRNAs are known to regulate about 2/3 of our genes and since their discovery they have been implicated in almost every physiological process. Thus, it is not a surprise to find alterations of miRNA expression linked to several pathological conditions, including CRC. However, the role of miRNAs in CRC carcinogenesis is far from being completely understood. A clearer comprehension of these players in CRC would contribute to better understand this pathology and unveil new biomarkers for CRC detection and/or clinical management. Here we propose to study the patterns of miRNAs behaviour throughout disease progression. Our main goal was to identify stage specific miRNAs alterations that could act as novel biomarkers. For that, we aimed to investigate (i) miRNAs expression and methylation patterns across CRC development; (ii) the targets of the differentially expressed miRNAs in order to better understand their role in CRC progression; (iii) stage specific alterations that could characterize patients within each stage of disease and provide a more accurate patient subclassification, and (iv) miRNA expression and methylation as prognostic value for CRC patients. We found that the major miRNA deregulation events occur during Normal to Stage I transition, and are generally maintained throughout disease progression. Importantly, we show that alterations in both miRNAs expression and methylation were able to distinguish normal from malignant tissue and to predict patient’s outcome, which evidences their potential as CRC diagnostic and prognostic biomarkers.
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