Abstract 1450: Global changes in RBPs and mRNA interactions during prostate cancer progression

Abstract

Abstract Prostate cancer (PC) is a leading cause of cancer in men in the United States and worldwide, disproportionately affecting men of African ancestry. The etiology and molecular mechanism contributing to lethal human PC remain poorly understood. RNA binding proteins (RBPs) controlled all aspects of RNA biogenesis, and dysregulated RBPs are linked to human diseases, including cancer. However, the global changes in RBP-mRNA interactions during PC progression are unknown. Here, we have investigated the patterns of RBPs and polyA-mRNA interaction in the castration-sensitive LNCaP and castration-resistant C4-2 PC cell lines. Our enhanced-RNA interactome capture assay combined with mass spectroscopy (MS) revealed that LNCaP and C4-2 cells showed distinct RBP-mRNA interaction patterns in steady-state and androgen-treated conditions. Also, we have studied the interaction between Yes-associated protein 1 (YAP1) and nucleophosmin (NPM1) RBP. Androgen increased NPM1 and mRNA interaction, and NPM1 is part of the YAP1 multiprotein complex, as revealed by MS-based proteomics approaches. Our proximity ligation assay showed that androgen hormone signaling regulated the interaction between YAP1 and NPM1. Besides, our GST-pulldown demonstrated that NPM1 binds the proline-rich region domain of YAP1, whereas the WW/SH3 domain of YAP1 mediates the interaction in C4-2 cells. Genetic silencing of NPM1 reduced PC cell growth in culture. Furthermore, the upregulation of NPM1 correlates with prostate adenocarcinoma and metastasis. These observations suggest that changes in RBP and RNA interaction patterns may play a critical role in PC progression and recurrence. Citation Format: Abdulrahman M. Dwead, Marwah M. Al-Mathkour, Bekir Cinar. Global changes in RBPs and mRNA interactions during prostate cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1450.