Role of Astrocyte Elevated Gene 1 and Exostosin 1 in Colon Cancer

Abstract

Background: AEG-1 (Astrocyte Elevated Gene-1) is a multifunctional protein that regulates a variety of cancers, including colon cancer, through interacting with other proteins. The goal of this research was to explore the effect of silencing AEG-1 and to understand how it regulates cell proliferation, apoptosis, angiogenesis, migration and invasion through interaction with Exostosin-1 (EXT-1) in colon cancer. newlineMaterials and Methods: Using bioinformatic tools, data on AEG-1 interacting proteins were retrieved and their interaction networks were assessed. Forward siRNA transfection using AEG-1 siRNA was performed in colon cancer cell lines and their mRNA and protein expression levels were measured using real-time PCR and immunofluorescence assay. AOM/DSS-induced BALB/c mice model was used for validating the effect of AEG-1 siRNA and EXT-1 siRNA. IHC staining was performed on paired control and tumor human colon tissue sections to validate the expression pattern of AEG-1 and EXT-1. newlineResults: Forward AEG-1 siRNA transfection significantly suppressed AEG-1 expression whereas, interestingly, EXT-1 expression was significantly upregulated in AEG-1 siRNA treated cells. Results from IHC of mouse tissues as well as human colon tissue sections indicated that the expression pattern of AEG-1 negatively correlated with that of EXT-1. newlineConclusions: The above results conferred that silencing AEG-1 might interfere indirectly with EXT-1 expression through PTCH-1 intermediate via the crosstalk between PI3K/AKT/mTOR and Hedgehog, thereby affecting cell-ECM interactions leading to decreased proliferation and invasion. Collectively, from this data, AEG-1 might be a potential therapeutic target in colon cancer and more clinical studies are needed in this direction newline newline