Gene expression-based, whole genome-wide expression profile differences for CUL4B-depleted LNCaP cells compared with control

Cancer stem-like traits contribute to prostate cancer (PCa) progression and metastasis. Discovering and clarifying the underlying molecular mechanisms associated with PCa stem-like traits would be great beneficial to clinical treatment of advanced PCa. Cullin 4B (CUL4B) is a scaffold protein overexpressed in several solid malignancies. It is known to silence tumor suppressor through post-transcriptional manner. In this study, through gain- and loss-of-function experiments, we showed that CUL4B promotes PCa pluripotency-associated markers expression, sphere formation and anchorage-independent growth ability in virto. Mechanically, we identified BMI1 as a target of CUL4B. CUL4B unregulates BMI1 expression via epigenetically repressing microRNA-200b (miR200b) and microRNA-200c (miR200c). In addition, miR200b and miR200c (miR200b/c) could partially reverse CUL4B-induced BMI1 and pluripotency-associated marker expression. Finally, our study revealed a CUL4B-miR200b/c-BMI1 oncoprotein axis in PCa, which might give novel insight into how CUL4B promotes PCa progression through regulating cancer stem-like traits. We carried out gene expression profiling in PCa using LNCaP cells with siRNA transfection vs. Negative control. The interference efficiency was verified by Real-Time PCR (qPCR) and western blot. Differentially expressed genes were identified based on standard and advanced quality control metrics (Fold change >2.0 and P-values <0.05). We found that there were 525 downregulated genes and 619 upregulated in CUL4B siRNA-transfected LNCaP cells.