Downregulation of NONO Suppresses Proliferation, Migration, and Invasion in Metastatic Prostate Cancer

As prostate cancer (PCa) remains one of the leading causes of cancer-related death in men, it is important to develop effective therapeutic approaches for the treatment of metastatic PCa and to improve the accuracy of prognosis for aggressive tumors. Non-POU domain-containing octamer-binding (NONO) is involved in RNA transport and almost all steps of gene regulation, and aberrant expression is associated with tumorigenesis in various tumor entities.

Immunohistochemical analysis of the expression of NONO was performed in a cohort of 405 patient samples, including 54 benign prostate tissues, 250 primary prostate tumors, and 101 metastatic tissue samples. To assess the role of NONO in PCa cells, siRNA-mediated knockdown of NONO in the metastatic PCa cell lines PC3 and DU145, followed by a series of functional assays including proliferation, transwell, western blotting, and real-time quantitative PCR, was used.

The current study showed that the nuclear expression of NONO increases during the progression of PCa and is highest in distant metastases. NONO regulates cell proliferation by increasing the expression of cell cycle-related genes. In addition, NONO modulates migration and invasion in PCa cells.

Overall, these results suggest inhibition of NONO may be a promising approach for the treatment of metastatic PCa.