Minimally Invasive Urology Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250012, China; School of Medicine, Shandong University, Jinan, 250012, China.
Minimally Invasive Urology Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250012, China.
Biomed Pharmacother. 2018 Oct;106:309-315. doi: 10.1016/j.biopha.2018.06.058. Epub 2018 Jul 11.
We investigated the regulatory function of HECT, UBA and WWE domain-containing protein 1, E3 ubiquitin protein ligase (HUWE1) in human prostate cancer (CaP).
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.
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.
HUWE1 overexpression could functionally suppress CaP development bothin vitro and in vivo, possibly by inverse regulation on c-Myc.
我们研究了 HECT、UBA 和 WWE 结构域包含蛋白 1（E3 泛素蛋白连接酶）在人前列腺癌（CaP）中的调节功能。
通过转染过表达或慢病毒转导下调 HUWE1 在前列腺癌细胞系 PC3 和 DU145 中的表达。检测 HUWE1 过表达或下调对 CaP 癌细胞体外增殖、迁移和体内外植体的影响。此外，还评估了 HUWE1 对 c-Myc 表达的调节作用。在 HUWE1 过表达的 CaP 细胞中，进一步上调 c-Myc 以评估 c-Myc 是否直接参与 HUWE1 诱导的 CaP 调节。
HUWE1 过表达抑制 CaP 体外增殖和迁移以及体内外植体生长。另一方面，HUWE1 下调对 CaP 无影响。在 HUWE1 过表达的 CaP 细胞中 c-Myc 下调，但在 HUWE1 下调的 CaP 细胞中不变。进一步上调 HUWE1 过表达的 CaP 细胞中的 c-Myc，逆转了 HUWE1 过表达对体外癌症增殖和迁移的肿瘤抑制作用。
HUWE1 过表达可在体内外功能性地抑制 CaP 的发展，可能通过对 c-Myc 的反向调节。
