Background: Cullin 4B (CUL4B), a scaffold protein that assembles CRL4B ubiquitin ligase complexes, is overexpressed in many types of solid tumors and contributes to epigenetic silencing of tumor suppressors. However, its clinical significance and underlying molecular mechanisms in prostate cancer (PCa) remain unknown.
Methods: The clinical significance of CUL4B in PCa was characterized by in silico method. RT-qPCR and Western blot were used to study the transcript and protein expression levels of CUL4B and C-MYC. Bioinformatics tools, chromatin immunoprecipitation (ChIP) and luciferase reporter assay were utilized to identify and characterize the microRNAs (miRNAs) regulated by CUL4B. The biological function of CUL4B and miR-33b-5p was evaluated by MTS, transwell, and wound healing assays, accordingly.
Results: CUL4B is significantly overexpressed in PCa tissues compared with benign prostatic tissues and its overexpression is correlated with poor prognosis. CUL4B promotes proliferation and aggressiveness of PCa cells in vitro. Mechanistically, we demonstrate that CUL4B upregulates the expression of C-MYC at post-transcriptional level through epigenetic silencing of miR-33b-5p. Importantly, CUL4B-induced oncogenic activity in PCa by targeting C-MYC is repressed by miR-33b-5p.
Conclusions: Our results suggested a novel CUL4B/miR-33b/C-MYC axis implicated in PCa cell growth and progression. This might provide novel insight into how CUL4B contributed to PCa aggressiveness and progression.
Keywords: C-MYC; CUL4B; miR-33b; progression; prostate cancer.
© 2019 Wiley Periodicals, Inc.