Competing Endogenous RNA (ceRNA) Networks Implicated in Prostate Cancer Progression to Castration Resistance Identified Through Bioinformatics Analyses

Abstract Purpose: Long non-coding RNAs (lncRNAs) regulate several biochemical pathways and contribute to the pathophysiology of cancer. In previous analyses, we identified 27 lncRNAs whose expression respond to hormone therapy in prostate cancer patients. Furthermore, in castration-resistant prostate cancer (CRPC), their levels were restored to those observed in therapy-naïve primary tumors. Nevertheless, lncRNAs contribution in tumorigenesis is still not understood. Since one mechanism of action of lncRNAs is acting as sponges of miRNAs, our main goal was to identify lncRNA-miRNA-mRNA networks altered during prostate cancer progression. Methods: We performed a bioinformatics-based analysis using public datasets comprising 40 primary prostate tumors (11 paired pre- and post-androgen deprivation therapy (ADT) and 29 pre-ADT) and 8 CRPC. We used miRNet (a miRNA-centric network visual analytics platform) to seek miRNAs that target both lncRNAs and mRNAs, and constructed ceRNA networks. Results: We identified 105 mRNAs differentially expressed in both post- vs pre-ADT primary tumors and CRPC vs post-ADT. We found that PCGEM1 (lncRNA) expression correlates with ASPM (mRNA) expression (r=0.51, p=8.2E-13), and these two RNAs have target sequences for the binding of hsa-miR-506-3p and hsa-miR-124-3p. These results identified a possible PCGEM1-hsa-miR-506-3p/hsa-miR-124-3p-ASPM ceRNA involved in prostate cancer progression to castration resistance. Other ceRNAs identified included RAB3B mRNA (RAS oncogene family) and are: PCGEM1-hsa-miR-124-3p-RAB3B, LINC01087-hsa-miR-130a-3p-RAB3B, and LINC01671-hsa-miR-145-5p-RAB3B. Conclusion: These results give new insights in ceRNA dysregulation in prostate cancer; and ultimately, they might help to identify new prognostic biomarkers for prostate cancer and new druggable targets for avoiding/delaying progression to CRPC. Citation Format: Sabrina Ledesma-Bazan, Florencia Cascardo, Juan Bizzotto, María Sol Ruiz, Elba Vazquez, Geraldine Gueron, Javier Cotignola. Competing Endogenous RNA (ceRNA) Networks Implicated in Prostate Cancer Progression to Castration Resistance Identified Through Bioinformatics Analyses [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 25.