S151 Examination of Downregulated miRNAs and Associated Pathways in Colorectal Cancer: A Systematic Review

Abstract

Introduction: Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Many biological molecules play a significant role in the pathogenesis of CRC including miRNAs, small RNA molecules that regulate the translation and stability of specific target mRNAs. Given the involvement of miRNAs on all fronts of CRC including pathogenesis, diagnosis, prognosis and potential therapy, it is imperative to fully understand their role within this deadly disease. With this study, we examined unique miRNAs which were upregulated in patients with CRC. Methods: We searched PubMed and the Cochrane Database of Systematic Reviews (CDSR) through Wiley from 2016 to 2022 for keywords “miRNA”,” micro-RNA”, “colon cancer”, “colorectal cancer”, “CRC”. From this data, we performed computational analysis using MicroInspector, miRanda, PicTar, RNA22, DIANA, softwares and identified unique upregulated miRNAs. We further examined the list of the biological pathways identified from predicted target genes of downregulated miRNAs and selected the top 4 pathways of clinical significance. We then filtered common miRNAs between these selected pathways and identified unique miRNAs between the top 4 pathways. Results: Through our computational analysis, we identified 59 upregulated miRNAs from studies of patients with CRC. We then identified a list of the biological pathways identified from downregulated miRNAs target genes. We also highlighted the relevant pathways which are associated with cancer including: MAPK signaling pathway (p -value 2.79 E-08), ErbB signaling (p-value 6.69E-08), PI3K-Akt (p-value 2.87E-06). We further investigated the highlighted pathways and found unique miRNAs associated with these pathways. Namely, hsa-mir-296-3p and hsa-mir-198-3p were identified, suggesting that these miRNAs may play an important role in those pathways. (Table) Conclusion: MicroRNAs play an important role in CRC initiation, progression, and development through manipulation of cell stemness, angiogenesis, apoptosis, and the epithelial–mesenchymal transition (EMT) of tumor cells. With this study we identified unique clinically relevant metabolic pathways of CRC affected by downregulated miRNAs. We also identified the unique miRNAs hsa-mir-296b-3p and hsa-mir-198-3p. Further work is necessary to identify specific roles of these miRNA candidates as biological markers or therapeutic targets for patients with CRC. Table 1. - List of the biological pathways identified from predicted target genes of downregulated miRNAs Pathway p-value #genes #miRNAs ECM-receptor interaction 4.97E-32 58 23 Proteoglycans in cancer 6.89E-12 124 26 Focal adhesion 5.81E-09 137 27 MAPK signaling pathway 2.79E-08 158 26 ErbB signaling pathway 6.69E-08 60 25 Renal cell carcinoma 4.80E-07 49 25 Axon guidance 1.08E-06 83 27 Regulation of actin cytoskeleton 2.17E-06 129 27 PI3K-Akt signaling pathway 2.87E-06 197 28 Rap1 signaling pathway 3.71E-06 127 26