Computational analysis of data from a genome-wide screening identifies new PARP1 functional interactors as potential therapeutic targets.

Computational analysis of data from a genome-wide screening identifies new PARP1 functional interactors as potential therapeutic targets. Oncotarget. 2019 Apr 12;10(28):2722-2737 Authors: Lodovichi S, Mercatanti A, Cervelli T, Galli A Abstract Knowledge of interaction network between different proteins can be a useful tool in cancer therapy. To develop new therapeutic treatments, understanding how these proteins contribute to dysregulated cellular pathways is an important task. PARP1 inhibitors are drugs used in cancer therapy, in particular where DNA repair is defective. It is crucial to find new candidate interactors of PARP1 as new therapeutic targets in order to increase efficacy of PARP1 inhibitors and expand their clinical utility. By a yeast-based genome wide screening, we previously discovered 90 candidate deletion genes that suppress growth-inhibition phenotype conferred by PARP1 in yeast. Here, we performed an integrated and computational analysis to deeply study these genes. First, we identified which pathways these genes are involved in and putative relations with PARP1 through g:Profiler. Then, we studied mutation pattern and their relation to cancer by interrogating COSMIC and DisGeNET database; finally, we evaluated expression and alteration in several cancers with cBioPortal, and the interaction network with GeneMANIA. We identified 12 genes belonging to PARP1-related pathways. We decided to further validate RIT1, INC...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research