TP53 Inhibited AR Signaling Promote Enzalutamide Resistance in LNCaP cell

Background: To perform gene screening and search key knockout gene associated with enzalutamide resistance in LNCaP cells. Methods: : Genome-scale CRISPR-Cas9 transfection were done to screen genes associated with enzalutamide resistance in LNCaP cells. Bioinformatic analysis of TP53 and AR expression correlated with prostate adenocarcinoma by using TCGA database. Knockout interfering RNA (shRNA) were synthesized in lentivirus and transfected into LNCaP cells by using Lipofectamine 3000. TP53 and AR detection was performed by using conventional molecular biology methods, such as western blot, RT-PCR and flow cytometer et al. Results: : 27 high (NES<-1.7, P1.7, P<0.01) expressed genes were identified in enzalutamide resistance Cells. TP53 interacted with AR may play an important role in the development of enzalutamide resistance from PPI and RNA-seq data. Data from TCGA support that patient with TP53&AR low expression endured higher pathology stage, Gleason grades, more disease progress, recurrence, positive lymphnotes examination numbers and more abnormal bones scan results. LNCaP cell dealt with enzalutamide or with TP53 knockout showed inhibited cell cycle at G0~G1, increased apoptosis percentage and also inhibited cell proliferation. Conclusions: : Current data support that TP53 protein inhabiting AR signaling promote enzalutamide resistance in LNCaP cell.