PO-051 GNL1 regulates cell proliferation by associating with RPS20

Abstract

analysed and clinically relevant candidates were validated in human tissue samples. The therapeutic potential of some candidates was evaluated in pre-clinical mouse models. Results and discussions Based on the H/L ratio, 2012 proteins were identified and quantified using the MaxQuant software. 168 proteins were found to be significantly (p-value<0.05) differentially expressed in LNCaP AI cells compared to LNCaP AD cells. Gene Ontology (GO) analysis of the highly differentially expressed upregulated proteins showed that the most enriched biological process was 'cell division', suggesting that higher expression of cell cycle genes may contribute to the progression of PCa to androgen independence. Gene expression of the top candidates was further validated in vitro. Protein expression levels of the key mitotic candidates was assessed in silico and by immunohistochemistry in a cohort of PCa patient samples (including CRPC tissues). In general, Mphase genes had preferentially higher staining patterns in aggressive PCa, indicating that mitotic regulators might play a role in the progression of PCa to a castration-resistant stage. Inhibition of 3 mitotic candidates resulted in reduced proliferation of PCa cells both in vitro and in vivo. Conclusion Key mitotic regulators are upregulated in androgen independent PCa and could be considered promising therapeutic targets for the molecular intervention of CRPC patients.