Computational Discovery of AngiomiRs and Evaluating the Synergistic Effects of Target miRNA with Tranexamic Acid in Colorectal Cancer

Abstract

Introduction: microRNA (miRNA) levels are dysregulated in many cancers, suggesting that miRNA-based therapy may be effective. The molecular pathways of colorectal cancer (CRC) development are unknown. Method: Understanding miRNAs implicated in CRC formation may reveal new diagnostic and therapeutic targets. Angiogenesis is a key mechanism in tumor growth. CRC treatment may involve inhibiting angiogenesis, but existing drugs can cause negative effects. Tranexamic acid, an FDA-approved medication, may reduce the adverse effects of angiogenesis inhibitors. This work examined miRNAs implicated in CRC angiogenesis and how miR-16 and tranexamic acid may synergistically decrease CRC cell migration and angiogenesis. We identified miRNAs targeting CRC angiogenesis genes using bioinformatic databases. Proteins were docked with tranexamic acid utilizing the PyRx software. Quantitative Real-time PCR was used to analyze the effects of overexpressed miRNA and tranexamic acid on the expression of target genes. Scratch, transwell migration, and Chicken Chorioallantoic Membrane (CAM) assays were used to evaluate the effect of selected miRNA and tranexamic acid on the invasion and angiogenesis of CRC cells. in silico studies identified hsa-miR-16-5p, -101-3p, and 34a-5p as possible CRC angiogenesis modulators. Results: The study found that miR-16 and tranexamic acid influence the expression of VEGFA, ANGPT2, MMP9, and HIF1A. miR-16 and tranexamic acid influenced CRC cell movement in scratch tests and transwell migration assays. Furthermore, the CAM assay results demonstrated that miR-16 and tranexamic acid can alter angiogenesis in CRC. Conclusion: These findings highlight the potential of miR-16 and tranexamic acid as combination therapeutic agents for CRC, with the ability to simultaneously target tumorigenesis and angiogenesis.