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SPAG9 promotes prostate cancer growth and metastasis
Authors:Chunhua YANG  Ye TIAN
Affiliation:1Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China2 Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China3 Suzhou Key Laboratory for Radiation Oncology, Suzhou, China
Abstract:Sperm-associated antigen 9 (SPAG9) expression is increased in prostate tissues of prostate cancerpatients. This experimental study aimed to investigate the role of SPAG9 in bone metastasis of prostate cancer.Immunohistochemical analysis showed that SPAG9 staining was positive in 81.67% of 240 cases of prostatic carcinomabut only in 6.67% of 120 cases of benign prostate hyperplasia. Strong PAG9 staining was positively correlated withGleason score and bone metastasis in 240 prostate cancer patients (p < 0.05), but not with the age or serum prostatespecific antigen level (p > 0.05). PC-3 cells were transfected with shRNA against SPAG9, and CCK-8 assay in triplicateshowed that PC-3 cell viability was inhibited by SPAG9 knockdown. In addition, transwell assay in triplicate showedthat PC-3 cell invasion was inhibited by SPAG9 knockdown. Furthermore, total 2 × 106 PC-3 cells were injectedsubcutaneously into the right flank of nude mice which were randomly divided into three groups (N = 8) and treatedby intratumoral injection of SPAG9 shRNA, control shRNA or PBS, respectively. SPAG9 shRNA inhibited thegrowth, invasion and angiogenesis while promoted apoptosis of xenografted PC-3 cells. SPAG9 knockdown led to theupregulation of E-cadherin and the downregulation of MMP2 and vimentin in xenografted tumors. In conclusion,this is the first study to provide evidence that SPAG9 promotes bone metastasis of prostate cancer, and SPAG9 is apromising target to prevent or treat bone metastasis of prostate cancer.
Keywords:Angiogenesis   Bone metastasis   Invasion   Prostate cancer   SPAG9
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