HUWE1 upregulation has tumor suppressive effect in human prostate cancer cell lines through c-Myc

Purpose: We investigated the regulatory function of HECT, UBA and WWE domain-containing protein 1, E3 ubiquitin protein ligase (HUWE1) in human prostate cancer (CaP). Methods: HUWE1 was overexpressed (through transfection) or downregulated (through lentiviral transduction) in CaP cell lines, PC3 and DU145 cells. The functions of HUWE1 overexpression or downregulation on CaP cancer cell proliferation, migrationin vitro, and explant in vivo were examined. In addition, the regulatory effect of HUWE1 on c-Myc expression was assessed. In HUWE1-overexpressed CaP cells, c-Myc was further upregulated to assess whether c-Myc was directly involved in HUWE1-induced regulation in CaP. Results: HUWE1 overexpression inhibited CaP proliferation and migrationin vitro, and explant growth in vivo. On the other hand, HUWE1 downregulation had no effects on CaP in vitro. C-Myc was downregulated in HUWE1-overexpressed, but un-changed in HUWE1-downregulated, CaP cells. Further upregulating c-Myc in HUWE1-overexpressed CaP cells reversed the tumor-suppressing effects by HUWE1-overexpression on cancer proliferation and migration in vitro. Conclusion: HUWE1 overexpression could functionally suppress CaP development both in vitro and in vivo, possibly by inverse regulation on c-Myc.