Target Fishing and Therapeutic Interventions Against Hepatocellular carcinoma (HCC) Using Bioinformatics Approaches

Abstract

Hepatocellular carcinoma (HCC) is the 5th most common type of cancer and, the 2nd cause of cancer death in adult males after lung cancer. It contains 90% of the primary carcinoma of the liver. There is no proper treatment available except surgeries and chemotherapies. This necessitates a better understanding of the underlying mechanisms of the therapeutic targets and interventions for the treatment of HCC. In the case of HCC, reactivation of telomerase expression increases the risk by about 90% and it involves the uncontrolled cell proliferation of HSC cells. Previously various HCC drugs have failed in clinical investigation mainly due to poor efficacy and target-disease linkage. Therefore, the identification of potential drug targets and their impact on the biological response could aid in the potential therapeutic intervention against HCC. Therefore, the construction of a biological regulatory network of previously known biomarkers in HCC and their responses were simulated. Subsequently, dynamic simulations were performed by JIMENA software using two types of cells (normal and diseased) under different concentrations of nodes. This study reveals that EGFR along with any combination might be used as a therapeutic target for HCC. This research indicates the upregulation of hTERT, EGFR, and ADRB-2 receptors and the downregulation of p53 and DYRK-3 in HCC. Significantly, crucial cellular components such as ADRB-2, AKT, and ERK display increased levels of activity when subjected to disturbance in diseased cells, indicating their possible involvement in the development of HCC. The nodes associated with apoptosis are inhibited, while cell proliferation reaches its peak activity after applying perturbation function, suggesting a possible imbalance that promotes excessive cell growth and inhibits the normal process of cell death in the disease condition. Key components in the advancement of cancer, including DYRK3, EGFR, and hTERT, exhibit substantial modifications, suggesting their possible role as catalysts in the behavior of abnormal cells. The triggering of SP1 introduces intricacy to the regulatory framework of the network. In this study, different therapeutic targets have been identified and their impact on the overall cellular response against hepatocellular carcinoma using systems biology approaches.