Identification of a STAT2 transcriptome in HCT116 p53 null tumor xenografts

Our previous study revealed that the transcription factor STAT2 promoted the growth of colorectal tumors, but the molecular mechanisms by which STAT2 contributes to tumor promotion are still unknown. Given that alterations in the tumor suppressor p53 gene are very common in colorectal cancer and critical in adenoma-carcinoma transition, we investigated whether STAT2 may also be implicated in disease progression when normal p53 function is disabled. We found Stat2 silencing in colon cancer cells deficient in p53 reduced the capacity of tumor cells to migrate and invade in vitro. We also determined that Stat2 silencing impaired tumor cells to metastasize to the liver. To begin to understand how STAT2 contributes to disease progression, we performed RNA-Seq analysis on colon tumor xenografts with the purpose to identify a STAT2 transcriptome. From this study, we identified a subset of STAT2 regulated genes that in future studies will confirm their role in colon carcinogenesis. We silenced Stat2 expression by shRNA approach in human p53 null HCT116 colorectal cancer cells. As a negative control, we used shRNA scrambled vector control. Subcutaneous tumor xenografts were generated in individual Rag1KO mice with these two cell lines. At day 21, we harvested tumors from 3 individual mice per cell line and submitted for transcriptomic profiling via RNA-Seq analysis. We compared transcriptomes between shSTAT2 and shControl tumors. Each data point represents an individual tumor (n-3).