Project description: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.
Project description:Global definition of androgen and anti-androgen effects on LNCaP transcriptomes using Affymetrix U133A oligonucleotide microarray. LNCaP in androgen-depleted medium was treated with androgen (DHT) and anti-androgen (CPA) for different time points (2 hours, 4 hours, 8 hours, and 24 hours). Untreated or Vehicle (Ethanol) treated samples as control.
Project description:Androgen receptor (AR) plays a critical role in prostate cancer onset and progression, and cell cycle and apoptosis regulator 1 (CCAR1) functions as an AR co-activator. We performed genome-wide gene expression analysis in control (shNS) and CCAR1-depleted (shCCAR1) LNCaP cells to assess the global effect of CCAR1 on the expression of androgen responsive genes.
Project description:Expression data from DHT stimulation vs. control in LNCaP cells LNCaP cells were maintained in phenol red-free RPMI supplemented with 10% charcoal/dextran stripped FCS for three days before stimulation with 100 nM dihydrotestosterone (DHT) for 48 hours