CUL4B regulates cancer stem-like traits of prostate cancer cells by targeting BMI1 via miR200b/c

Background: Cancer stem-like traits contribute to prostate cancer (PCa) progression and metastasis. Cullin 4B (CUL4B) is a member of the ubiquitin E3 ligase family and overexpressed in several solid malignancies including PCa. CUL4B has been suggested to be an oncogene through epigenetic repression of tumor suppressors. However, the link between CUL4B expression and cancer stem-like phenotype remains unclear.

Methods: Western blot analysis, sphere formation, and colony formation assays were used to examine the effect of CUL4B on cancer stem-like traits in PCa cells. Mechanically, bioinformatic analysis was utilized to evaluate whether BMI1 was a target of CUL4B. Moreover, real-time polymerase chain reaction, chromatin immunoprecipitation, and luciferase reporter assays were performed to identify microRNAs regulated by CUL4B. Finally, Western blot assay was used to validate the regulation of CUL4B, miR200b, and miR200c (miR200b/c) on the stem-like characteristics of PCa cells.

Results: CUL4B promotes PCa pluripotency-associated markers expression, sphere formation, and anchorage-independent growth ability in vitro. Mechanically, CUL4B upregulates BMI1 expression via epigenetically repressing miR200b/c expression. In addition, miR200b/c could partially reverse CUL4B-induced BMI1 and pluripotency-associated marker expression.

Conclusions: Our study revealed that CUL4B regulates cancer stem-like traits of prostate cancer cells by targeting BMI1 via miR200b/c, which might give novel insight into how CUL4B promotes PCa progression through regulating cancer stem-like traits.