Grant: Travel Awards - Institute Community Support

Prostate cancer (PCa) is the most prevalent cancer diagnosis among men worldwide and the fifth leading cause of cancer-related mortality in the male population. Hence, it is essential to understand the molecular mechanisms driving the pathogenesis of this disease that will help to develop improved therapeutic strategies. Nucleoli are membraneless condensates within the nucleus of a cell that play essential roles in various cellular processes, including rRNA transcription, splicing, and ribosome biogenesis. Previous research has shown that the nucleoli are heavily involved in the increased ribosome production and protein synthesis required for cancer growth. In fact, enlarged nucleoli are a characteristic of castration-resistant prostate cancer (CRPC), a difficult to treat and aggressive PCa subtype with poor survival rate. In this study, we investigate the function of Lysine Rich Nucleolar Protein 1 (KNOP1), a nucleolar protein, expressed at higher levels in CRPC patient tissues. We use a combination of molecular, cellular, and imaging tools for our investigation. Our preliminary findings show that KNOP1 is an essential regulator of nucleolar organization and functions. Silencing of KNOP1 in CRPC cells altered the morphology of the nucleolus- the nucleoli became fused in KNOP1 silenced cells compared to a dispersed state in the control cells. Moreover, silencing of KNOP1 reduced rRNA transcription, mRNA translation and protein synthesis in CRPC cells. Additionally, the KNOP1 silenced CRPC cells were found to be less proliferative compared to control CRPC cells or normal prostatic cells. Furthermore, KNOP1 has a potential role in binding RNAs that suggests its role in the regulation of gene expression, RNA processing, and post-transcriptional regulation. As a critical regulator of CRPC nucleolar morphology and function, investigating KNOP1 regulation and function are beneficial to understand the molecular mechanism behind the disease's development and progression.