Executive Summary : | Hepatocellular carcinoma (HCC) is a prevalent and fatal liver cancer, with a rapidly increasing incidence and mortality rate worldwide, including in India. The disease is caused by various factors, including Hepatitis B Virus, Hepatitis C Virus, Aflatoxin, and excessive alcoholism. Non-alcoholic steatohepatitis (NASH) is the major causing factor, and obesity contributes more to simple fatty liver, progressed NASH, and hepatocarcinogenesis. The molecular mechanisms underlying HCC development and progression are poorly understood, making it crucial to identify new players involved in telomerase regulation for the development of novel therapeutic targets and biomarkers. Currently, there are no effective treatments for HCC, and few drugs have failed due to side effects. This study aims to study the regulation, expression, and activity of telomerase enzyme in human HCC cells, tissues, and a mouse model of xenograft tumor. The hypothesis is that RISC components are significantly overexpressed in HCC cells and tissues, and Telomerase expression and activity are positively correlated with RISC activity in HCC. The study also aims to determine the synergistic role of RISC components and Telomerase in HCC development using human HCC cells, tissue, and a mouse xenograft tumor. Therapeutic intervention targeting RISC complex and Telomerase using Withaferin A, Quercetin, and RNA interference approaches will be used against human HCC cells and in a mouse model of xenograft tumor. The successful completion of this project will help translate the synergistic effect of RISC and Telomerase as diagnostic and therapeutic targets, potentially saving lives for HCC patients who currently lack effective therapies. |