GSE203120
Chemical genomic screen identifies SP2509, WT hTERT specific repressor in colorectal cancer
Telomerase is necessary for cell immortality in cancer. Hence, during tumerognesis cancer cells reactivates telomerase to attain uncotrolled proliferation. There are no clinically approved drugs available to inhibit telomerase in cancer. We performed a chemical screen using a novel endogenous hTERT reported cell line and identified a compound, SP2509 which acts specifically in cancer cells immortalised by WT TERT activity. Further we identified that Pirin is a molecular target of the compund and it regulate the level of SP1, an important transcriptional activator of WT TERT gene. We finally show iron dependency of pirin to activate TERT in CRC cell lines. Overall design: HCT116 cells are treated with SP2509 for 48 hrs and/or transiently knockdowned for Pirin using siRNA for 48 hrs. Following the treatment cells, RNA isolation was done using Trizol and DNase treated using M&N RNA mini kit and purified using mini columns