The role of super enhancer-controlled genes in colon cancer

Sammanfattning

Developing a wide array of therapeutic agents increases the likelihood that patients will survive cancer and continue their lives with limited side effects. It is common knowledge that cancer is caused by mutated DNA resulting in uncontrolled cell growth, but it is less widely recognized that enhancer regions also lead to tumor development. More research is needed to understand how super enhancers act as regulators of several oncogenes and could serve as targets for cancer treatment.The aim of the project was to investigate the effects of super enhancers on cancer cell growth and test the effect of inhibitors as a potential treatment option. For this purpose, MYC proto-oncogene bHLH transcription factor (MYC), SRY-box transcription factor 9 (SOX9) and KIT ligand (KITLG) were selected as prototype super enhancer-controlled genes. They were studied in more detail through reverse transcription quantitative polymerase chain reaction (RT-qPCR) and RNA fluorescence in situ hybridization (RNA FISH) in the HCT 116 cell line, epithelial cells from a colon cancer cell line with a particular Kirsten rat sarcoma virus (KRAS) mutation. Finally, the effect of A485, JQ1 and BI2865, three different inhibitors were tested and respective gene expression measured.Results showed that gene expression of all three super enhancer-controlled genes increased by 2.7 times when the cancer cells were stimulated to grow. Results also confirmed that JQ1 and A485 reduced gene expression of the selected genes by 7 and 15-fold respectively, however more research was necessary to confirm their clinical use in the fight against cancer.