HoxB3 promotes prostate cancer cell progression by transactivating CDCA3

Homeobox (Hox) genes encode homeodomain-containing transcription factors critical to development, differentiation, and homeostasis. Their dysregulation has been implicated in various cancers. In the present study, we show that HoxB3 mRNA and protein are overexpressed in primary prostate cancer tissues compared to the adjacent normal prostate tissues. Moreover, HoxB3 overexpression is associated with higher Gleason grade (⩾7) (P = 0.002), clinical stage (P < 0.001) and PSA level (⩾10) (P = 0.013). The Kaplan and Meier analysis showed that HoxB3 overexpression predicts poor survival outcome. Overexpression of HoxB3 promotes LNCaP cells proliferation and migration in vitro. Furthermore, depletion of HoxB3 in PC-3 cells decreased the capacity of proliferation in a cell division cycle associated 3 (CDCA3)-dependent manner both in vitro and in vivo. The ChIP analysis indicates that HoxB3 can bind to the CDCA3 promoter region and transactivate the CDCA3 expression. These data suggested that HoxB3 promote prostate cancer progression by upregulating CDCA3 expression and may serve as a potential therapeutic target for human prostate cancer.

► HoxB3 is over-expression in primary prostate cancer and predicts poor outcome.
► Up-regulation or down-regulation of HoxB3 promotes or inhibits prostate cancer cell proliferation and migration.
► HoxB3 promotes prostate cancer cell progression by transactivating CDCA3.