Significance of the nuclear Insulin-like Growth Factor Receptor-1 in Liver Cancer

Liver cancer ranks as the sixth most prevalent cancer in terms of incidence. Nearly 90% of primary liver cancers are hepatocellular carcinomas (HCC), which have grown to be a serious health issue on a global scale. The study focused on investigating the insulin-like growth receptor-1 in the liver cancer cells, HepG2. In HCC, IGF-1R is highly expressed and induces drug resistance by promoting cell motility, proliferation, and anti-apoptosis through the PI3K/ Akt and RAS/ RAF/ ERF signalling pathways. In various cancer types, the IGF-1R typically found on cell membranes is predominantly located in the cell nucleus, and its presence there is associated with poor prognosis. Our study corroborates the previously reported ChIP-seq findings, contributing to the understanding of nuclear IGF-1R's role in various biological processes, including the regulation of transcription. We characterised the gene regulatory network of nuclear IGF-1R via bioinformatic analysis to define its potential targets. We overexpressed and knocked down IGF-1R in HepG2 cells to validate several genes identified by ChIP-seq analysis. These are the novel IGF-1R potential targets that have not yet been investigated in the context of HepG2 cells. In conclusion, these findings may lead to the identification of novel targetable mechanisms regulated by IGF-1R in hepatic carcinoma.