Figure 2

MicroRNAome profiling reveals pathways associated with prostate cancer biology and identifies miR-100-5p association with ADT. (A) Identification of candidate miRNAs that were up-regulated during the post-castration period and in both CRPC/NEPC relapses. microRNA-specific microarray was performed on hormone-naive (LTL-313B/-331), post-castrated (LTL-313BCx/-331Cx), and relapse (LTL-313BR/-331R) in PCa PDX progression models for CRPC and NEPC, respectively. microRNAs with a fold change of >2.0 compared to LTL-313B/-331 were identified as being up-regulated for post-castration in both models (dormancy-associated microRNAs; DAM), CRPC relapse (CRPC-associated microRNAs; CAM), or NEPC relapse (NEPC-associated microRNAs; NAM). microRNAs that were specifically up-regulated during the post-castration period and in both relapses were determined by overlapping DAM, CAM, and NAMs. (B) Top representative canonical pathways associated with LTL-313B and LTL-331 PDX models. microRNA microarray analysis of hormone sensitive and insensitive PDX models reveals miR-100-5p being consistently expressed, and upregulated in both CRPC (LTL-313B) and NEPC (LTL-331) fated tumors post therapy. (C,D) miR-100-5p is upregulated in vivo upon androgen ablation (host castration) in both CRPC and NEPC fated tumors. Mature microRNA expression from the MIR100HG cluster are also evaluated in LTL-313B/-331 castration (Cx) series (pre-Cx, post-Cx, relapse) via qPCR. (E) miR-100-5p expression was measured in 11 representative pre- and post-Cx PCa PDX models via qPCR.