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.
CONCLUSION: 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.