effect of depletion of PRCAT71 and KHSRP on gene expression in prostate cancer cells

Mounting evidence indicates that long non-coding RNAs (lncRNAs) play vital roles in tumorigenesis and progression of cancers. However, the functions and regulatory mechanisms of lncRNAs in prostate cancer (PCa) are still largely unknown. In this study, we discovered a PCa-specific lncRNA, PRCAT71, significantly highly expressed in metastatic and primary PCa compared to benign prostate tissues. Silencing PRCAT71 inhibited cancerous properties of PCa cells, as well as androgen receptor (AR) signaling. Mechanismly, PRCAT71 acts as a scaffold to recruit KH-type splicing regulatory protein (KHSRP) to AR mRNA and stabilize AR mRNA. Furthermore, PRCAT71 is transcriptionally regulated by AR, thus forming a positive regulatory loop between AR and PRCAT71 in PCa. Our findings demonstrate that the PRCAT71-KHSRP-AR axis is a promising therapeutic target to treat PCa. Overall design: Comparative gene expression profiling analysis of RNA-seq data for LNCaP cells stably expressing shRNA targeting PRCAT71/shRNA control, or for C4-2 cells stably expressing shRNA targeting KHSRP/shRNA control.