RNA-Seq analysis of Trim28-deleted NPp53 mouse prostate tissue
Tripartite motif-containing 28 (TRIM28/TIF1b/KAP1) is a key transcriptional co-repressor protein that represses ERV expression in many cell types including embryonic stem cells, neural progenitor cells, differentiated adult cells, and cancer cells. In this study, we investigated the effect of Trim28 deletion on the expression of ERVs using an immune competent genetically engineered mouse model for prostate cancer. We found Trim28 deletion in prostate tumors led to the expression of ERVs in prostates from both hormonally intact and castrated mice. ERVs can regulate the expression of neighboring genes, and we detected increased expression of several protein-coding genes near overexpressed ERVs. Our data suggest that Trim28 deletion in prostate tumor epithelial cells may promote an innate immune response. However, Trim28 deletion also led to excessive deposition of tumor extracellular matrix (ECM). Our findings suggest that ECM alterations downstream of ERV derepression could affect immune cells in the tumor microenvironment and may promote tumor progression. Overall design: RNA-Seq expression profiles from NPp53 (Pten;Tp53 deleted) and NPp53T (Pten;Tp53; Trim28 deleted) mouse prostates