title: 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.
abstract: 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.
authors.affiliation: Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Mitsunari
authors.affiliation: Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. Electronic address: int.doc.miya@m3.dion.ne.jp.
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Miyata
authors.affiliation: Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Asai
authors.affiliation: Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Matsuo
authors.affiliation: Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Shida
authors.affiliation: Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Hakariya
authors.affiliation: Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Sakai
mesh_terms: D000368:Aged; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D000067780:ELAV-Like Protein 1 / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology; D011237:Predictive Value of Tests; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*
chemical_list: D000067780:ELAV-Like Protein 1; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2