Progression of Non-Alcoholic Fatty Liver Disease to Hepatocellular Carcinoma: the Cell Death Pathways

Markandan, Mangala Rubbini (2022) Progression of Non-Alcoholic Fatty Liver Disease to Hepatocellular Carcinoma: the Cell Death Pathways. Final Year Project (Bachelor), Tunku Abdul Rahman University College.

Text Mangala Rubbini_Full Text.pdf Restricted to Registered users only Download (3MB)

Abstract

Necroptosis is a programmed cell death form of necrosis that also occurs in hepatocytes of obese individuals that can potentially lead to severe scarring of liver tissues (cirrhosis) and liver cancer. The main purpose of this study is to construct molecular pathways of the crucial proteins involved in necroptotic cell death based on published data that causes progression of Non-Alcoholic Fatty Liver Disease (NAFLD) to Hepatocellular Carcinoma (HCC). Softwares such as BioRender and CellDesigner are used in this study to illustrate cell death pathways that lead to the progression of NAFLD to HCC. The necroptosis pathways constructed are categorized into (i) inhibition of caspase-8, (ii) mitochondrial dysfunction and (iii) TAK1 activation in the absence of Tab2 cell death. Ligands such as Fas, TNF-α and TRAIL play a role in necroptosis initiation which lead to the further activation of RIP1, RIP3, and MLKL. In this research, several target proteins that could be inhibited to minimize the progression of NAFLD to HCC were identified. The target proteins are RIP3 and MLKL. RIP3 and MLKL proteins are identified as target proteins as they are involved in all the necroptosis pathways constructed in this study and inhibition of these proteins may stop necroptosis from occurring. To date, mechanism of necroptosis in liver cancer is still poorly understood. In view of this, discovery of cell death pathways in this research enabled information to be conveyed in a simpler and more comprehensive format. This work could create a better understanding of the target proteins that regulate necroptosis, which further aids the development of novel therapy for liver cancer.