Role of miRNAs in Sigmoid Colon Cancer: A Search for Potential Biomarkers

SIMPLE SUMMARY: Understanding the microRNAs’ role in cancer is challenging, because, in the most cases, the only tissues available are the tumor and its counterpart, the adjacent-to-tumor tissue. Indeed, this scenario could affect our analyses in the cancer field, including to colorectal cancer. Using systematic criteria to select the healthy individuals and sigmoid colon cancer cases, we found that adjacent-to-tumor tissue already has molecular alterations in relation to healthy tissue and to tumor tissue as well. In addition, all miRNAs found showed to be involved in the carcinogenic process, according to the gene enrichment analysis. We suggested that future cancer studies should consider using these three tissues in their analysis, as well as the creation of a database of healthy individuals’ miRNA expression profiles. Using these three tissues, we could better understand the role of adjacent-to-tissue in cancer and other several questions related with clinical aspects. ABSTRACT: The aberrant expression of microRNAs in known to play a crucial role in carcinogenesis. Here, we evaluated the miRNA expression profile of sigmoid colon cancer (SCC) compared to adjacent-to-tumor (ADJ) and sigmoid colon healthy (SCH) tissues obtained from colon biopsy extracted from Brazilian patients. Comparisons were performed between each group separately, considering as significant p-values < 0.05 and |Log(2)(Fold-Change)| > 2. We found 20 differentially expressed miRNAs (DEmiRNAs) in all comparisons, two of which were shared between SCC vs. ADJ and SCC vs. SCH. We used miRTarBase, and miRTargetLink to identify target-genes of the differentially expressed miRNAs, and DAVID and REACTOME databases for gene enrichment analysis. We also used TCGA and GTEx databases to build miRNA-gene regulatory networks and check for the reproducibility in our results. As findings, in addition to previously known miRNAs associated with colorectal cancer, we identified three potential novel biomarkers. We showed that the three types of colon tissue could be clearly distinguished using a panel composed by the 20 DEmiRNAs. Additionally, we found enriched pathways related to the carcinogenic process in which miRNA could be involved, indicating that adjacent-to-tumor tissues may be already altered and cannot be considered as healthy tissues. Overall, we expect that these findings may help in the search for biomarkers to prevent cancer progression or, at least, allow its early detection, however, more studies are needed to confirm our results.