Human antigen R is positively associated with malignant aggressiveness via upregulation of cell proliferation, migration, and vascular endothelial growth factors and cyclooxygenase-2 in prostate cancer
详细信息 查看全文
- 作者：Kensuke Mitsunari ; Yasuyoshi Miyata ; int.doc.miya@m3.dion.ne.jp" class="auth_mail" title="E-mail the corresponding author ; Akihiro Asai ; Tomohiro Matsuo ; Yohei Shida ; Tomoaki Hakariya ; Hideki Sakai
- 关键词：BCR ; biochemical recurrence ; COX ; cyclooxygenase ; CRPC ; castration-resistant prostate cancer ; HO ; heme oxygenase ; HuR ; human antigen-R ; IRS ; immunoreactive score ; KD ; knockdown ; PCa ; prostate cancer ; PSA ; prostate-specific antigen ; RP ; radical prostatectomy ; VEGFs ; vascular endothelial growth factors ; WT ; wild type
- 刊名：Translational Research
- 出版年：2016
- 出版时间：September 2016
- 年：2016
- 卷：175
- 期：Complete
- 页码：116-128
- 全文大小：2871 K
文摘
Limited information is available on the pathologic significance of human antigen R (HuR) in prostate cancer (PCa). The main aim of this study was to clarify the relationship between HuR expression and malignant aggressiveness, outcome, and expression of cancer-related molecules in PCa. In vitro proliferation, colony formation, and migration assays were performed on LNCaP and PC-3 cells. HuR expression was knocked down (KD) using small interfering RNA. The relationships between HuR expression and the expression of vascular endothelial growth factors (VEGFs), cyclooxygenase (COX)-2, and heme oxygenase (HO)-1 were investigated in PCa cell lines using Western blotting. On KD of HuR, cell proliferation and migration were suppressed in both LNCaP and PC-3 cells, whereas expression of VEGF-A to -D and COX-2 was suppressed in PC-3 but not in LNCaP cells. In addition, expression of these cancer-related factors was analyzed in 182 hormone-naïve PCa and 23 castration-resistant prostate cancer (CRPC) human tissues in vivo. Cytoplasmic (C)-HuR expression was significantly higher in CRPC > hormone-naïve PCa > nontumoral cells. C-HuR expression was positively associated with Gleason score, T stage, and metastasis, and it was considered to be a useful predictor of biochemical recurrence after radical prostatectomy. C-HuR expression was correlated with COX-2 expression in hormone-naïve PCa, and with the expression of VEGF-A, VEGF-C, and COX-2 in CRPC tissues. Our results demonstrated that HuR plays important roles in determining malignant aggressiveness and outcome in PCa, especially in androgen-independent PCa cells, via the regulation of cell proliferation, migration, and expression of VEGF-A, -C, and COX-2.