Ppar-Responsive Elements Enriched With Alu Repeats May Contribute To Distinctive Ppar Gamma-Dnmt1 Interactions In The Genome

Background: PPAR gamma (peroxisome proliferator-activated receptor gamma) is involved in the pathology of numerous diseases, including UM and other types of cancer. Emerging evidence suggests that an interaction between PPAR gamma and DNMTs (DNA methyltransferase) plays a role in cancer that is yet to be defined. Methods: The configuration of the repeating elements was performed with CAP3 and MAFFT, and the structural modelling was conducted with HDOCK. An evolutionary action scores algorithm was used to identify oncogenic variants. A systematic bioinformatic appraisal of PPAR gamma and DNMT1 was performed across 29 tumor types and UM available in The Cancer Genome Atlas (TCGA). Results: PPAR-responsive elements (PPREs) enriched with Alu repeats are associated with different genomic regions, particularly the promotor region of DNMT1. PPAR gamma -DNMT1 co-expression is significantly associated with several cancers. C-terminals of PPAR gamma and DNMT1 appear to be the potential protein-protein interaction sites where disease-specific mutations may directly impair the respective protein functions. Furthermore, PPAR gamma expression could be identified as an additional prognostic marker for UM. Conclusions: We hypothesize that the function of PPAR gamma requires an additional contribution of Alu repeats which may directly influence the DNMT1 network. Regarding UM, PPAR gamma appears to be an additional discriminatory prognostic marker, in particular in disomy 3 tumors.