AT-rich interactive domain 5B regulates androgen receptor transcription in human prostate cancer cells

Background: The androgen receptor (AR) is one of the most important and dynamically regulated factors in prostate cancer (PCa) progression. Despite the importance of AR expression regulation, the precise mechanisms are not fully understood. ARID5B, an AT-rich interaction domain DNA-binding motif-containing transcription factor, is expressed higher in primary PCa than normal prostate, and correlated with AR expression. We therefore hypothesized that ARID5B could regulate AR expression.

Methods: Correlation between AR and ARID5B expression was analyzed using publicly and commercially available microarray data. To examine the role of ARID5B in AR expression, ARID5B was knocked down in VCaP and LNCaP cells, then mRNA and protein levels of AR were measured and an in vitro cell proliferation assay was performed. Chromatin immunoprecipitation was performed to further examine molecular mechanisms.

Results: Knockdown of ARID5B suppressed the AR mRNA and protein expression in VCaP and LNCaP cells and decreased in vitro cell proliferation. Suppression of ARID5B decreased the occupancy of active RNA polymerase II in the AR promoter, indicating that ARID5B regulates AR transcription. The active histone mark, H3K4me3, occupancy was decreased with ARID5B knockdown.

Conclusion: Our study revealed that AR transcription is positively regulated by ARID5B through H3K4me3 recruitment in the AR promoter. Our findings reveal novel mechanisms of AR transcription, which is dynamically regulated in prostate tumor progression.