BioProject

Previous studies have demonstrated that deletion of Cryptochromes (CRY) protects p53-/- mutant mice from early onset of cancer and extends their median lifespan by about 1. More...

Previous studies have demonstrated that deletion of Cryptochromes (CRY) protects p53-/- mutant mice from early onset of cancer and extends their median lifespan by about 1.5 fold. In vitro studies had revealed that deletion of CRY enhances apoptosis in response to UV damage through activation of p73, and inactivation of GSK3β. However, it was not known at the transcriptome-wide level how CRY deletion delays the onset of cancer in p53-/- mutant mice. In this study, an RNA-seq approach was taken to identify the differentially regulated genes and pathways in p53-/- and p53-/-Cry1-/-Cry2-/- mouse embryonic fibroblasts following UV-induced DNA damage. Gene Set Enrichment Analysis demonstrated that immune surveillance associated genes regulated by IFN-γ showed increased responses, as well as genes involved in TNFα signaling via NF-κB. Protein network analysis helped identify key genes such as p21, Egr3, Sirt1, Jun and Casp1 among differentially regulated genes, and revealed their interaction partners. Collectively, the present study suggests that additional genes involved in NF-κB regulation, IFN-γ response, as well as non-coding RNAs may contribute to delaying the onset of cancer in p53-/-Cry1-/-Cry2-/- mice compared to p53-/- mutant mice. Overall design: Polyadenylated RNA profiles of mouse embryonic fibroblasts from p53-/- and p53-/-Cry1-/-Cry2-/- knockout mice either UV treated or not treated, in two biological replicates, obtained using Illumina HiSeq 2500 platform Less...