title: miR-539 inhibits prostate cancer progression by directly targeting SPAG5.
abstract: BACKGROUND
  We conducted multiple microarray datasets analyses from clinical and xenograft tumor tissues to search for disease progression-driving oncogenes in prostate cancer (PCa). Sperm-associated antigen 5 (SPAG5) attracted our attention. SPAG5 was recently identified as an oncogene participating in lung cancer and cervical cancer progression. However, the roles of SPAG5 in PCa progression remain unknown.
  
  
  METHODS
  SPAG5 expression level in clinical primary PCa, metastatic PCa, castration resistant PCa, neuroendocrine PCa, and normal prostate tissues was investigated. We established multiple in vivo xenografts models using patient-derived tissues and investigated SPAG5 expression trend in these models. We also investigated the functions of SPAG5 in vivo and in vitro studies. Luciferase reporter assays were performed to investigate potential miRNAs that can regulate SPAG5.
  
  
  RESULTS
  We identified that SPAG5 expression was gradually increased in PCa progression and its level was significantly associated with lymph node metastasis, clinical stage, Gleason score, and biochemical recurrence. Our results indicated that SPAG5 knockdown can drastically inhibit PCa cell proliferation, migration, and invasion in vitro and supress tumor growth and metastasis in vivo. We identified that miR-539 can directly target SPAG5. Ectopic overexpression of miR-539 can drastically inhibit SPAG5 expression and the restoration of SPAG5 expression can reverse the inhibitory effects of miR-539 on PCa cell proliferation and metastasis.
  
  
  CONCLUSIONS
  Our results collectively showed a progression-driving role of SPAG5 in PCa which can be regulated by miR-539, suggesting that miR-539/SPAG5 can serve as a potential therapeutic target for PCa.
authors.affiliation: Department of Urology, National Key Specialty of Urology, Second Hospital of Tianjin Medical University, Tianjin Key Institute of Urology, Tianjin Medical University, Tianjin, China.|Vancouver Prostate Centre & Department of Urologic Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Hongtuan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Vancouver Prostate Centre & Department of Urologic Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.|Department of Urology, Chengdu military general hospital, Chendu, Sichuan, China.
authors.forename: Shadan
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Urology, National Key Specialty of Urology, Second Hospital of Tianjin Medical University, Tianjin Key Institute of Urology, Tianjin Medical University, Tianjin, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Urology, National Key Specialty of Urology, Second Hospital of Tianjin Medical University, Tianjin Key Institute of Urology, Tianjin Medical University, Tianjin, China.
authors.forename: Baomin
authors.initials: B
authors.lastname: Qiao
authors.affiliation: Department of Urology, National Key Specialty of Urology, Second Hospital of Tianjin Medical University, Tianjin Key Institute of Urology, Tianjin Medical University, Tianjin, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Urology, National Key Specialty of Urology, Second Hospital of Tianjin Medical University, Tianjin Key Institute of Urology, Tianjin Medical University, Tianjin, China. xymnwk@163.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
mesh_terms: D020413:3' Untranslated Regions; D018797:Cell Cycle Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D060787:Neoplasm Grading; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D020413:3' Untranslated Regions; D018797:Cell Cycle Proteins; C552081:MIRN539 microRNA, human; D035683:MicroRNAs; C486663:SPAG5 protein, human
keywords: Progression; Prostate cancer; SPAG5; miR-539; miRNA