PO-326 Impact of miR-205–5 p and miR-425–5 p on Wnt and AR signalling pathways in castration resistant prostate cancertransition

Introduction Prostate cancer (PCa) is the second leading cause of cancer mortality in western countries. Prostate tumours initially respond well to androgen-deprivation therapy (ADT). Unfortunately, the majority of tumours evolve, after androgen deprivation, from a hormone-sensitive to a castration-resistant prostate cancer (CRPC). For that reason new agents, targeting the androgen receptor (AR) pathway (abiraterone, enzalutamide among others), have been approved in the last decade. Unfortunately, the emergence of resistance to these treatments is common and CPRC remains highly lethal. Therefore, new approaches and better knowledge of the molecular mechanisms leading to CRPC is still needed. Mechanisms related to CRPC transition include increased expression of AR and activating mutations in this receptor. As in other tumours, there are other signalling pathways that could interfere with AR activation such as Wnt signalling pathway, which has been suggested to play an important role in CRPC. On the other hand, emerging evidences indicate that certain miRNAs are involved in the appearance of treatment resistances in several diseases. The aim of this project was to study miRNA and mRNA expression profiles to identify deregulated miRNAs and genes involved in the Wnt signalling pathway in CRPC. Material and methods A set of 20 PCa tumour samples, 10 radical prostatectomy (RP) specimens from hormone-naive patients vs 10 transurethral resection of prostate (TURP) samples from castration resistant patients, were analysed. Total RNA was obtained to study miRNA and mRNA expression using Affymetrix GeneChip miRNA 4.0 and GeneChip Clariom S human arrays, respectively. To identify deregulated miRNAs and their corresponding predicted target mRNA related to AR and Wnt signalling pathways, both miRNA and mRNA expression profiles were integrated by correlation analysis using the TAC software (appliedbiosystems). Results and discussions When hormone-naive samples vs. castration-resistant samples were compared, 62 miRNAs and 1023 mRNAs were significantly deregulated. Further identification of potential target genes found a strong correlation between hsa-miR-205–5 p, AR and Wnt5A, and between hsa-miR425-5p and GSK3β. In addition, expression of hsa-miR-425–5 p correlated with survival (2-tailed Student’s t test, p-value Conclusion Integrated analysis of miRNA and mRNA expression profiles is a useful tool to identify novel therapeutic targets for CPRC. The role of miRNAs involved in CRPC deserves further investigation.