Browsing by Author "Dwaed, Abdulrahman"

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PROTEOMICS ANALYSIS OF RNA BINDING PROTEINS IN PROSTATE CANCER CELLS
(Clark Atlanta University, 2024-03-26) Dwaed, Abdulrahman; Cinar, Bekir
RNA-binding proteins (RBPs) govern various RNA-related functions, and dysregulation of RBPs is linked to numerous human diseases, including cancer. RBPs regulate the intricate facets of RNA biogenesis, impacting its metabolism and functional kinetics. This study investigates the biochemical and functional interactions between the RNA-binding protein NPM1 and the Hippo pathway effector of the transcriptional coregulatory protein YAP1. This study also examined the system-wide changes in RBP patterns in prostate cancer cell lines with differential responses to androgen hormone signaling. This study revealed that androgen hormone signaling regulates the protein-protein interaction of YAP1 with NPM1. GST-pulldown assay combined with western blot showed that the proline-rich region and WW/SH3 domain of YAP1 mediated the interaction with NPM1. The proximity ligation assay combined with co-immunoprecipitation further verified the interaction between YAP1 and NPM1 in the androgen-dependent (AD) and androgen-independent (AI) cell lines. Disruption of NPM1 activity by genetic and pharmacological approaches reduced cell growth and cell migration in cultures, likely mediated by the inhibition of YAP1. Moreover, treatment of AD and AI cells with or without androgen resulted in distinct RBP patterns, as demonstrated by enhanced RNA interactome capture assay combined with quantitative mass spectroscopy-based proteomics. Furthermore, the analysis of prostate cancer tissues showed an elevated NPM1 expression that correlated with prostate tumor progression. These findings suggest that altered RBP patterns downstream of modified androgen hormone signaling contribute to tumor progression, and the YAP1-NPM1 axis may constitute a viable drug target in cancer.
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