WD repeat domain 5 promotes chemoresistance and Programmed Death-Ligand 1 expression in prostate cancer

• DOI: 10.7150/thno.55814
• Publication Date: 2021-03-16T06:06:20Z
• Authors: Qianghua Zhou; Xu Chen; Haixia He; Shengmeng Peng; Yangjie Zhang; Jingtong Zhang; Liang Cheng; Sen Liu; Ming Huang; Ruihui Xie; Tianxin Lin; Jian Huang
• Keywords: Chromatin immunoprecipitation; H3K4me3

Purpose: Advanced prostate cancer (PCa) has limited treatment regimens and shows low response to chemotherapy immunotherapy, leading poor prognosis. Histone modification is a vital mechanism of gene expression promising therapy target. In this study, we characterized WD repeat domain 5 (WDR5), regulator histone modification, explored its potential therapeutic value in PCa. Experimental Design: We specific regulators based on TCGA data. The clinical features WDR5 were analyzed two dependent cohorts. functional role was further investigated with siRNA OICR-9429, small molecular antagonist WDR5, vitro vivo. by RNA-sequencing chromatin immunoprecipitation (ChIP). Results: overexpressed PCa associated advanced clinicopathological features, predicted Both inhibition OICR-9429 could reduce proliferation, increase apoptosis chemosensitivity cisplatin Interestingly, targeting block IFN-γ-induced PD-L1 cells. Mechanistically, clarified that some cell cycle, anti-apoptosis, DNA repair immune related genes, including AURKA, CCNB1, E2F1, PLK1, BIRC5, XRCC2 PD-L1, directly regulated H3K4me3 c-Myc manner. Conclusions: These data revealed suppressed enhanced apoptosis, immunotherapy Therefore, our findings provide insight into multi-potency drug, which improves the antitumor effect or