USING GENE-miRNA NETWORKS ANALYSIS TO IDENTIFY POSSIBILITIES IN CURRENTLY AVAILABLE MEDICATIONS FOR CHRONIC HEPATITIS-INDUCED HCC

Abstract

This report presents a detailed bioinformatics investigation into the molecular underpinnings of chronic hepatitis-induced Hepatocellular Carcinoma (HCC), aiming to identify significantly differentially expressed genes (DEGs) and microRNAs (miRNAs) and to pinpoint therapeutic drugs that can modulate these dysregulated networks. Utilizing public gene expression datasets (e.g., GSE121248) and bioinformatics tools, the analysis revealed a distinct molecular landscape critical to HCC progression. The study identified a comprehensive list of the 10 most important downregulated genes, including key tumor suppressors like CDHR2, ACADS, and IGFBP3, alongside the 10 most important upregulated genes, such as SCN3B, OGG1, and KNOP1, many of which are associated with oncogenic processes. Furthermore, the report details the mechanisms of action and miRNA-modulating capabilities of several therapeutic agents. Cisplatin, a DNA-damaging chemotherapy, upregulates the tumor suppressor hsa-miR-34a, enhancing its cytotoxic effects. Sorafenib, a multi-kinase inhibitor, demonstrates a dual miRNA-modulating role by upregulating tumor-suppressive let-7 family members while downregulating the oncogenic hsa-miR-21-5p. In contrast, Regorafenib and Everolimus, while highly effective kinase and mTOR inhibitors respectively, do not directly target miRNAs but indirectly influence the gene-miRNA network by impacting genes that are themselves subject to miRNA regulation. This comprehensive analysis highlights the complex interplay within gene-miRNA networks in HCC pathogenesis and provides a mechanistic basis for how existing drugs influence these networks, offering insights for potentially enhancing therapeutic efficacy and overcoming resistance in HCC treatment.